Skip to main content
SpringerLink
Log in

Mitochondrial dynamics, positioning and function mediated by cytoskeletal interactions

  • Review
  • Published:
Cellular and Molecular Life Sciences Aims and scope Submit manuscript

Abstract

The ability of a mitochondrion to undergo fission and fusion, and to be transported and localized within a cell are central not just to proper functioning of mitochondria, but also to that of the cell. The cytoskeletal filaments, namely microtubules, F-actin and intermediate filaments, have emerged as prime movers in these dynamic mitochondrial shape and position transitions. In this review, we explore the complex relationship between the cytoskeleton and the mitochondrion, by delving into: (i) how the cytoskeleton helps shape mitochondria via fission and fusion events, (ii) how the cytoskeleton facilitates the translocation and anchoring of mitochondria with the activity of motor proteins, and (iii) how these changes in form and position of mitochondria translate into functioning of the cell.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Kühlbrandt W (2015) Structure and function of mitochondrial membrane protein complexes. BMC Biol 13:89

    Article  PubMed Central  PubMed  Google Scholar 

  2. Lee JH, Park A, Oh KJ et al (2019) The role of adipose tissue mitochondria: regulation of mitochondrial function for the treatment of metabolic diseases. Int J Mol Sci. https://doi.org/10.3390/ijms20194924

    Article  PubMed Central  PubMed  Google Scholar 

  3. Duchen MR (2000) Mitochondria and calcium: from cell signalling to cell death. J Physiol 529:57–68. https://doi.org/10.1111/j.1469-7793.2000.00057.x

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  4. Murphy MP (2009) How mitochondria produce reactive oxygen species. Biochem J 417:1–13

    Article  CAS  PubMed  Google Scholar 

  5. Wang C, Youle RJ (2009) The role of mitochondria in apoptosis*. Annu Rev Genet 43:95–118. https://doi.org/10.1146/annurev-genet-102108-134850

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  6. Zhang H, Menzies KJ, Auwerx J (2018) The role of mitochondria in stem cell fate and aging. Dev. 145(8):143420. https://doi.org/10.1242/dev.143420

  7. Palade GE (1953) An electron microscope study of the mitochondrial structure. J Histochem Cytochem 1:188–211. https://doi.org/10.1177/1.4.188

    Article  CAS  PubMed  Google Scholar 

  8. Sjostrand FS (1953) Electron microscopy of mitochondria and cytoplasmic double membranes. Nature 171:30–31

    Article  CAS  PubMed  Google Scholar 

  9. Ernster L, Schatz G (1981) Mitochondria: a historical review. J Cell Biol 91:227s–255s

    Article  CAS  PubMed  Google Scholar 

  10. Green DE (1951) The cyclophorase complex of enzymes. Biol Rev 26:410–453. https://doi.org/10.1111/j.1469-185X.1951.tb01205.x

    Article  CAS  Google Scholar 

  11. Schrepfer E, Scorrano L (2016) Mitofusins, from Mitochondria to Metabolism. Molecular Cell. 61: 683-694. https://doi.org/10.1016/j.molcel.2016.02.022

  12. Pagliuso A, Cossart P, Stavru F (2018) The ever-growing complexity of the mitochondrial fission machinery. Cell Mol Life Sci 75:355–374

    Article  CAS  PubMed  Google Scholar 

  13. Liu R, Chan DC (2015) The mitochondrial fssion receptor Mff selectively recruits oligomerized Drp1. Mol Biol Cell 26:4466–4477. https://doi.org/10.1091/mbc.E15-08-0591

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  14. Mozdy AD, McCaffery JM, Shaw JM (2000) Dnm1p GTPase-mediated mitochondrial fission is a multi-step process requiring the novel integral membrane component Fis1p. J Cell Biol 151:367–379. https://doi.org/10.1083/jcb.151.2.367

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  15. Shen Q, Yamano K, Head BP et al (2014) Mutations in Fis1 disrupt orderly disposal of defective mitochondria. Mol Biol Cell 25:145–159. https://doi.org/10.1091/mbc.E13-09-0525

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  16. Yu R, Jin S, Lendahl U et al (2019) Human Fis1 regulates mitochondrial dynamics through inhibition of the fusion machinery. EMBO J. https://doi.org/10.15252/embj.201899748

    Article  PubMed Central  PubMed  Google Scholar 

  17. Iwasawa R, Mahul-Mellier A-L, Datler C et al (2011) Fis1 and Bap31 bridge the mitochondria-ER interface to establish a platform for apoptosis induction. EMBO J 30:556–568. https://doi.org/10.1038/emboj.2010.346

    Article  CAS  PubMed  Google Scholar 

  18. Head B, Griparic L, Amiri M et al (2009) Inducible proteolytic inactivation of OPA1 mediated by the OMA1 protease in mammalian cells. J Cell Biol 187:959–966. https://doi.org/10.1083/jcb.200906083

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  19. Mishra P, Carelli V, Manfredi G, Chan DC (2014) Proteolytic cleavage of Opa1 stimulates mitochondrial inner membrane fusion and couples fusion to oxidative phosphorylation. Cell Metab 19:630–641. https://doi.org/10.1016/j.cmet.2014.03.011

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  20. MacVicar T, Langer T (2016) OPA1 processing in cell death and disease - the long and short of it. J Cell Sci 129:2297–2306

    Article  CAS  PubMed  Google Scholar 

  21. Ban T, Kohno H, Ishihara T, Ishihara N (2018) Relationship between OPA1 and cardiolipin in mitochondrial inner-membrane fusion. Biochim Biophys Acta Bioenerg 1859:951–957. https://doi.org/10.1016/j.bbabio.2018.05.016

    Article  CAS  PubMed  Google Scholar 

  22. Olichon A, Baricault L, Gas N et al (2003) Loss of OPA1 perturbates the mitochondrial inner membrane structure and integrity, leading to cytochrome c release and apoptosis. J Biol Chem 278:7743–7746. https://doi.org/10.1074/jbc.C200677200

    Article  CAS  PubMed  Google Scholar 

  23. Ge Y, Shi X, Boopathy S et al (2020) Two forms of opa1 cooperate to complete fusion of the mitochondrial inner-membrane. Elife. https://doi.org/10.7554/eLife.50973

    Article  PubMed Central  PubMed  Google Scholar 

  24. Tondera D, Czauderna F, Paulick K et al (2005) The mitochondrial protein MTP18 contributes to mitochondrial fission in mammalian cells. J Cell Sci 118:3049–3059. https://doi.org/10.1242/jcs.02415

    Article  CAS  PubMed  Google Scholar 

  25. Wikstrom JD, Mahdaviani K, Liesa M et al (2014) Hormone-induced mitochondrial fission is utilized by brown adipocytes as an amplification pathway for energy expenditure. EMBO J 33:418–436. https://doi.org/10.1002/embj.201385014

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  26. Motori E, Puyal J, Toni N et al (2013) Inflammation-induced alteration of astrocyte mitochondrial dynamics requires autophagy for mitochondrial network maintenance. Cell Metab 18:844–859. https://doi.org/10.1016/j.cmet.2013.11.005

    Article  CAS  PubMed  Google Scholar 

  27. Mehta K, Chacko LA, Chug MK et al (2019) Association of mitochondria with microtubules inhibits mitochondrial fission by precluding assembly of the fission protein Dnm1. J Biol Chem 294:3385–3396. https://doi.org/10.1074/jbc.RA118.006799

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  28. Mishra P, Chan DC (2014) Mitochondrial dynamics and inheritance during cell division, development and disease. Nat Rev Mol Cell Biol 15:634–646

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  29. Chacko LA, Mehta K, Ananthanarayanan V (2019) Cortical tethering of mitochondria by the anchor protein Mcp5 enables uniparental inheritance. J Cell Biol 218:3560–3571. https://doi.org/10.1083/jcb.201901108

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  30. Chang DTW, Honick AS, Reynolds IJ (2006) Mitochondrial trafficking to synapses in cultured primary cortical neurons. J Neurosci 26:7035–7045. https://doi.org/10.1523/JNEUROSCI.1012-06.2006

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  31. Ohno N, Kidd GJ, Mahad D et al (2011) Myelination and axonal electrical activity modulate the distribution and motility of mitochondria at CNS nodes of Ranvier. J Neurosci 31:7249–7258. https://doi.org/10.1523/JNEUROSCI.0095-11.2011

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  32. Rangaraju V, Calloway N, Ryan TA (2014) Activity-driven local ATP synthesis is required for synaptic function. Cell 156:825–835. https://doi.org/10.1016/j.cell.2013.12.042

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  33. Rangaraju V, Lauterbach M, Schuman EM et al (2019) Spatially stable mitochondrial compartments fuel local translation during plasticity article spatially stable mitochondrial compartments fuel local translation during plasticity. Cell 176:73-84.e15. https://doi.org/10.1016/j.cell.2018.12.013

    Article  CAS  PubMed  Google Scholar 

  34. Lees RM, Johnson JD, Ashby MC (2020) Presynaptic boutons that contain mitochondria are more stable. Front Synaptic Neurosci 11:37

    Article  PubMed Central  PubMed  Google Scholar 

  35. Sprenger HG, Langer T (2019) The good and the bad of mitochondrial breakups. Trends Cell Biol 29:888–900

    Article  CAS  PubMed  Google Scholar 

  36. Misgeld T, Schwarz TL (2017) Mitostasis in neurons: maintaining mitochondria in an extended cellular architecture. Neuron 96:651–666

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  37. Pollard TD (2007) Regulation of actin filament assembly by Arp2/3 complex and formins. Annu Rev Biophys Biomol Struct 36:451–477

    Article  CAS  PubMed  Google Scholar 

  38. Vignjevic D, Kojima SI, Aratyn Y et al (2006) Role of fascin in filopodial protrusion. J Cell Biol 174:863–875. https://doi.org/10.1083/jcb.200603013

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  39. Hatch AL, Gurel PS, Higgs HN (2014) Novel roles for actin in mitochondrial fission. J Cell Sci 127:4549–4560

    Article  PubMed Central  PubMed  Google Scholar 

  40. Wegner A, Isenberg G (1983) 12-fold difference between the critical monomer concentrations of the two ends of actin filaments in physiological salt conditions. Proc Natl Acad Sci U S A 80:4922–4925. https://doi.org/10.1073/pnas.80.16.4922

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  41. Pollard TD, Cooper JA (2009) Actin, a central player in cell shape and movement. Science 326:1208–1212

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  42. Heng YW, Koh CG (2010) Actin cytoskeleton dynamics and the cell division cycle. Int J Biochem Cell Biol 42:1622–1633

    Article  CAS  PubMed  Google Scholar 

  43. Lee Sweeney H, Holzbaur ELF (2018) Motor proteins. Cold Spring Harb Perspect Biol. https://doi.org/10.1101/cshperspect.a021931

    Article  PubMed  Google Scholar 

  44. Friedman JR, Lackner LL, West M et al (2011) ER tubules mark sites of mitochondrial division. Science 334:358–362. https://doi.org/10.1126/science.1207385

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  45. Lee JE, Westrate LM, Wu H et al (2016) Multiple dynamin family members collaborate to drive mitochondrial division. Nature 540:139–143. https://doi.org/10.1038/nature20555

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  46. Ji WK, Hatch AL, Merrill RA et al (2015) Actin filaments target the oligomeric maturation of the dynamin GTPase Drp1 to mitochondrial fission sites. Elife. https://doi.org/10.7554/eLife.11553

    Article  PubMed Central  PubMed  Google Scholar 

  47. Chada SR, Hollenbeck PJ (2004) Nerve growth factor signaling regulates motility and docking of axonal mitochondria. Curr Biol 14:1272–1276. https://doi.org/10.1016/j.cub.2004.07.027

    Article  CAS  PubMed  Google Scholar 

  48. Gutnick A, Banghart MR, West ER, Schwarz TL (2019) The light-sensitive dimerizer zapalog reveals distinct modes of immobilization for axonal mitochondria. Nat Cell Biol 21:768–777. https://doi.org/10.1038/s41556-019-0317-2

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  49. Boldogh IR, Pon LA (2006) Interactions of mitochondria with the actin cytoskeleton. Biochim Biophys Acta 1763:450–462. https://doi.org/10.1016/j.bbamcr.2006.02.014

    Article  CAS  PubMed  Google Scholar 

  50. Gourlay CW, Carpp LN, Timpson P et al (2004) A role for the actin cytoskeleton in cell death and aging in yeast. J Cell Biol 164:803–809. https://doi.org/10.1083/jcb.200310148

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  51. Breitenbach M, Laun P, Gimona M (2005) The actin cytoskeleton, RAS-cAMP signaling and mitochondrial ROS in yeast apoptosis. Trends Cell Biol 15:637–639. https://doi.org/10.1016/j.tcb.2005.10.004

    Article  CAS  PubMed  Google Scholar 

  52. Korobova F, Gauvin TJ, Higgs HN (2014) A role for myosin II in mammalian mitochondrial fission. Curr Biol 24:409–414. https://doi.org/10.1016/j.cub.2013.12.032

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  53. Franker MAM, Hoogenraad CC (2013) Microtubule-based transport -basic mechanisms, traffic rules and role in neurological pathogenesis. J Cell Sci 126:2319–2329. https://doi.org/10.1242/jcs.115030

    Article  CAS  PubMed  Google Scholar 

  54. Forth S, Kapoor TM (2017) The mechanics of microtubule networks in cell division. J Cell Biol 216:1525–1531

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  55. Tolić-Nørrelykke IM (2008) Push-me-pull-you: How microtubules organize the cell interior. Eur Biophys J 37:1271–1278. https://doi.org/10.1007/s00249-008-0321-0

  56. Woods LC, Berbusse GW, Naylor K (2016) Microtubules are essential for mitochondrial dynamics-fission, fusion, and motility-in Dictyostelium discoideum. Front Cell Dev Biol. https://doi.org/10.3389/fcell.2016.00019

    Article  PubMed Central  PubMed  Google Scholar 

  57. Fu C, Jain D, Costa J et al (2011) mmb1p binds mitochondria to dynamic microtubules. Curr Biol 21:1431–1439. https://doi.org/10.1016/j.cub.2011.07.013

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  58. Li T, Zheng F, Cheung M et al (2015) Fission yeast mitochondria are distributed by dynamic microtubules in a motor-independent manner. Sci Rep 5:11023. https://doi.org/10.1038/srep11023

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  59. Jourdain I, Gachet Y, Hyams JS (2009) The dynamin related protein Dnm1 fragments mitochondria in a microtubule-dependent manner during the fission yeast cell cycle. Cell Motil Cytoskeleton 66:509–523. https://doi.org/10.1002/cm.20351

    Article  CAS  PubMed  Google Scholar 

  60. Melkov A, Abdu U (2018) Regulation of long-distance transport of mitochondria along microtubules. Cell Mol Life Sci 75:163–176

    Article  CAS  PubMed  Google Scholar 

  61. Shen J, Zhang J-H, Xiao H et al (2018) Mitochondria are transported along microtubules in membrane nanotubes to rescue distressed cardiomyocytes from apoptosis. Cell Death Dis 9:81. https://doi.org/10.1038/s41419-017-0145-x

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  62. Hermann GJ, Shaw JM (1998) Mitochondrial dynamics in yeast. Annu Rev Cell Dev Biol 14:265–303. https://doi.org/10.1146/annurev.cellbio.14.1.265

    Article  CAS  PubMed  Google Scholar 

  63. Schwarz N, Leube R (2016) Intermediate filaments as organizers of cellular space: how they affect mitochondrial structure and function. Cells 5:30. https://doi.org/10.3390/cells5030030

    Article  CAS  PubMed Central  Google Scholar 

  64. Tang HL, Lung HL, Wu KC et al (2008) Vimentin supports mitochondrial morphology and organization. Biochem J 146:141–146. https://doi.org/10.1042/BJ20071072

    Article  CAS  Google Scholar 

  65. Milner DJ, Mavroidis M, Weisleder N, Capetanaki Y (2000) Desmin cytoskeleton linked to muscle mitochondrial distribution and respiratory function. J Cell Biol 150:1283–1297

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  66. Chernoivanenko IS, Matveeva EA, Gelfand VI, Goldman RD (2015) Mitochondrial membrane potential is regulated by vimentin intermediate filaments. FASEB J 29:820–827. https://doi.org/10.1096/fj.14-259903

    Article  CAS  PubMed  Google Scholar 

  67. Stone MR, O’Neill A, Lovering RM et al (2007) Absence of keratin 19 in mice causes skeletal myopathy with mitochondrial and sarcolemmal reorganization. J Cell Sci 120:3999–4008. https://doi.org/10.1242/jcs.009241

    Article  CAS  PubMed  Google Scholar 

  68. Kumar V, Bouameur JE, Bär J et al (2015) A keratin scaffold regulates epidermal barrier formation, mitochondrial lipid composition, and activity. J Cell Biol 211:1057–1075. https://doi.org/10.1083/jcb.201404147

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  69. Steen K, Chen D, Wang F, et al (2019) A role for keratins in supporting mitochondrial organization and function in skin keratinocytes. Mol Biol Cell 31:1103-1111. https://doi.org/10.1091/mbc.E19-10-0565

  70. Wiche G (1998) Role of plectin in cytoskeleton organization and dynamics. J Cell Sci 111:2477–2486

    Article  CAS  PubMed  Google Scholar 

  71. Wiche G, Winter L (2011) Plectin isoforms as organizers of intermediate filament cytoarchitecture. Bioarchitecture 1:14–20. https://doi.org/10.4161/bioa.1.1.14630

    Article  PubMed Central  PubMed  Google Scholar 

  72. Winter L, Kuznetsov AV, Grimm M et al (2015) Plectin isoform P1b and P1d deficiencies differentially affect mitochondrial morphology and function in skeletal muscle. Hum Mol Genet 24:4530–4544. https://doi.org/10.1093/hmg/ddv184

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  73. Reipert S, Steinböck F, Fischer I et al (1999) Association of mitochondria with plectin and desmin intermediate filaments in striated muscle. Exp Cell Res 252:479–491. https://doi.org/10.1006/excr.1999.4626

    Article  CAS  PubMed  Google Scholar 

  74. Mostowy S, Cossart P (2012) Septins: the fourth component of the cytoskeleton. Nat Rev Mol Cell Biol 13:183–194

    Article  CAS  PubMed  Google Scholar 

  75. Pagliuso A, Tham TN, Stevens JK et al (2016) A role for septin 2 in Drp1-mediated mitochondrial fission. EMBO Rep 17:858–873. https://doi.org/10.15252/embr.201541612

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  76. Twig G, Shirihai OS (2011) The interplay between mitochondrial dynamics and mitophagy. Antioxidants Redox Signal 14:1939–1951

    Article  CAS  Google Scholar 

  77. Lieber T, Jeedigunta SP, Palozzi JM et al (2019) Mitochondrial fragmentation drives selective removal of deleterious mtDNA in the germline. Nature 570:380–384. https://doi.org/10.1038/s41586-019-1213-4

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  78. Chen H, Vermulst M, Wang YE et al (2010) Mitochondrial fusion is required for mtdna stability in skeletal muscle and tolerance of mtDNA mutations. Cell 141:280–289. https://doi.org/10.1016/j.cell.2010.02.026

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  79. Smirnova E, Griparic L, Shurland DL, Van der Bliek AM (2001) Dynamin-related protein Drp1 is required for mitochondrial division in mammalian cells. Mol Biol Cell 12:2245–2256. https://doi.org/10.1091/mbc.12.8.2245

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  80. Legesse-Miller A, Massol RH, Kirchhausen T (2003) Constriction and Dnm1p recruitment are distinct processes in mitochondrial fission. Mol Biol Cell 14:1953–1963. https://doi.org/10.1091/mbc.E02-10-0657

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  81. Rehklau K, Hoffmann L, Gurniak CB et al (2017) Cofilin1-dependent actin dynamics control DRP1-mediated mitochondrial fission. Cell Death Dis 8:e3063. https://doi.org/10.1038/cddis.2017.448

    Article  PubMed Central  PubMed  Google Scholar 

  82. Li S, Xu S, Roelofs BA et al (2015) Transient assembly of F-actin on the outer mitochondrial membrane contributes to mitochondrial fission. J Cell Biol 208:109–123. https://doi.org/10.1083/jcb.201404050

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  83. Korobova F, Ramabhadran V, Higgs HN (2013) An actin-dependent step in mitochondrial fission mediated by the ER-associated formin INF2. Science 339:464–467. https://doi.org/10.1126/science.1228360

    Article  CAS  PubMed  Google Scholar 

  84. Manor U, Bartholomew S, Golani G et al (2015) A mitochondria-anchored isoform of the actin-nucleating spire protein regulates mitochondrial division. Elife. https://doi.org/10.7554/eLife.08828

    Article  PubMed Central  PubMed  Google Scholar 

  85. Curchoe CL, Manor U (2017) Actin cytoskeleton-mediated constriction of membrane organelles via endoplasmic reticulum scaffolding. ACS Biomater Sci Eng 3:2727–2732

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  86. Almutawa W, Smith C, Sabouny R et al (2019) The R941L mutation in MYH14 disrupts mitochondrial fission and associates with peripheral neuropathy. EBioMedicine 45:379–392. https://doi.org/10.1016/j.ebiom.2019.06.018

    Article  PubMed Central  PubMed  Google Scholar 

  87. Chakrabarti R, Ji WK, Stan RV et al (2018) INF2-mediated actin polymerization at the ER stimulates mitochondrial calcium uptake, inner membrane constriction, and division. J Cell Biol 217:251–268. https://doi.org/10.1083/jcb.201709111

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  88. Moore AS, Wong YC, Simpson CL, Holzbaur ELF (2016) Dynamic actin cycling through mitochondrial subpopulations locally regulates the fission-fusion balance within mitochondrial networks. Nat Commun 7:1–13. https://doi.org/10.1038/ncomms12886

    Article  CAS  Google Scholar 

  89. Lewis MR, Lewis WH (1915) Mitochondria (and other cytoplasmic structures) in tissue cultures. Am J Anat 17:339–401. https://doi.org/10.1002/aja.1000170304

    Article  Google Scholar 

  90. Martz D, Lasek RJ, Brady ST, Allen RD (1984) Mitochondrial motility in axons: Membranous organelles may interact with the force generating system through multiple surface binding sites. Cell Motil 4:89–101. https://doi.org/10.1002/cm.970040203

    Article  CAS  PubMed  Google Scholar 

  91. Carré M, André N, Carles G et al (2002) Tubulin is an inherent component of mitochondrial membranes that interacts with the voltage-dependent anion channel. J Biol Chem 277:33664–33669. https://doi.org/10.1074/jbc.M203834200

    Article  PubMed  Google Scholar 

  92. Ligon LA, Steward O (2000) Role of microtubules and actin filaments in the movement of mitochondria in the axons and dendrites of cultured hippocampal neurons. J Comp Neurol 427:351–361. https://doi.org/10.1002/1096-9861(20001120)427:3%3c351::AID-CNE3%3e3.0.CO;2-R

    Article  CAS  PubMed  Google Scholar 

  93. Wang Y, Huang Y, Liu Y et al (2018) Microtubule associated tumor suppressor 1 interacts with mitofusins to regulate mitochondrial morphology in endothelial cells. FASEB J 32:4504–4518. https://doi.org/10.1096/fj.201701143RR

    Article  CAS  PubMed  Google Scholar 

  94. Porat-Shliom N, Harding OJ, Malec L et al (2019) mitochondrial populations exhibit differential dynamic responses to increased energy demand during exocytosis in vivo. iScience 11:440–449. https://doi.org/10.1016/j.isci.2018.12.036

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  95. Chung JY-M, Steen JA, Schwarz TL (2016) Phosphorylation-induced motor shedding is required at mitosis for proper distribution and passive inheritance of mitochondria. Cell Rep 16:2142–2155. https://doi.org/10.1016/j.celrep.2016.07.055

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  96. Schuler M-H, Lewandowska A, Di CG et al (2017) Miro1-mediated mitochondrial positioning shapes intracellular energy gradients required for cell migration. Mol Biol Cell 28:2159–2169. https://doi.org/10.1091/mbc.e16-10-0741

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  97. Mills KM, Brocardo MG, Henderson BR (2015) APC binds the Miro/Milton motor complex to stimulate transport of mitochondria to the plasma membrane. Mol Biol Cell 27:466–482. https://doi.org/10.1091/mbc.e15-09-0632

    Article  PubMed  Google Scholar 

  98. Zhou B, Yu P, Lin M-Y et al (2016) Facilitation of axon regeneration by enhancing mitochondrial transport and rescuing energy deficits. J Cell Biol 214:103–119. https://doi.org/10.1083/jcb.201605101

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  99. Luchsinger LL, de Almeida MJ, Corrigan DJ et al (2016) Mitofusin 2 maintains haematopoietic stem cells with extensive lymphoid potential. Nature 529:528–531. https://doi.org/10.1038/nature16500

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  100. Mironov SL (2007) ADP regulates movements of mitochondria in neurons. Biophys J 92:2944–2952. https://doi.org/10.1529/biophysj.106.092981

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  101. Van Gestel K, Köhler RH, Verbelen J (2002) Plant mitochondria move on F-actin, but their positioning in the cortical cytoplasm depends on both F-actin and microtubules. J Exp Bot 53:659–667. https://doi.org/10.1093/jexbot/53.369.659

    Article  PubMed  Google Scholar 

  102. Sturmer K, Baumann O, Walz B (1995) Actin-dependent light-induced translocation of mitochondria and ER cisternae in the photoreceptor cells of the locust Schistocerca gregaria. J Cell Sci 108:2273–2283

    Article  PubMed  Google Scholar 

  103. Lawrence EJ, Boucher E, Mandato CA (2016) Mitochondria-cytoskeleton associations in mammalian cytokinesis. Cell Div 11:3. https://doi.org/10.1186/s13008-016-0015-4

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  104. Glater EE, Megeath LJ, Stowers RS, Schwarz TL (2006) Axonal transport of mitochondria requires milton to recruit kinesin heavy chain and is light chain independent. J Cell Biol 173:545–557. https://doi.org/10.1083/jcb.200601067

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  105. Morris RL, Hollenbeck PJ (1995) Axonal transport of mitochondria along microtubules and F-actin in living vertebrate neurons. J Cell Biol 131:1315–1326. https://doi.org/10.1083/jcb.131.5.1315

    Article  CAS  PubMed  Google Scholar 

  106. Pathak D, Sepp KJ, Hollenbeck PJ (2010) Evidence that myosin activity opposes microtubule-based axonal transport of mitochondria. J Neurosci 30:8984–8992. https://doi.org/10.1523/JNEUROSCI.1621-10.2010

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  107. Venkatesh K, Mathew A, Koushika SP (2020) Role of actin in organelle trafficking in neurons. Cytoskeleton 77:97–109. https://doi.org/10.1002/cm.21580

    Article  CAS  PubMed  Google Scholar 

  108. Boldogh IR, Yang HC, Dan Nowakowski W et al (2001) Arp2/3 complex and actin dynamics are required for actin-based mitochondrial motility in yeast. Proc Natl Acad Sci U S A 98:3162–3167. https://doi.org/10.1073/pnas.051494698

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  109. Senning EN, Marcus AH (2010) Actin polymerization driven mitochondrial transport in mating S cerevisiae. Proc Natl Acad Sci 107:721–725. https://doi.org/10.1073/pnas.0908338107

    Article  PubMed  Google Scholar 

  110. Itoh T, Watabe A, Toh-E A, Matsui Y (2002) Complex formation with Ypt11p, a rab-type small GTPase, is essential to facilitate the function of Myo2p, a class V myosin, in mitochondrial distribution in Saccharomyces cerevisiae. Mol Cell Biol 22:7744–7757

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  111. Itoh T, Toh-E A, Matsui Y (2004) Mmr1p is a mitochondrial factor for Myo2p-dependent inheritance of mitochondria in the budding yeast. EMBO J 23:2520–2530. https://doi.org/10.1038/sj.emboj.7600271

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  112. Altmann K, Frank M, Neumann D et al (2008) The class V myosin motor protein, Myo2, plays a major role in mitochondrial motility in Saccharomyces cerevisiae. J Cell Biol 181:119–130. https://doi.org/10.1083/jcb.200709099

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  113. Lewandowska A, MacFarlane J, Shaw JM (2013) Mitochondrial association, protein phosphorylation, and degradation regulate the availability of the active Rab GTPase Ypt11 for mitochondrial inheritance. Mol Biol Cell 24:1185–1195. https://doi.org/10.1091/mbc.E12-12-0848

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  114. Fehrenbacher KL, Boldogh IR, Pon LA (2005) A role for Jsn1p in recruiting the Arp2/3 complex to mitochondria in budding yeast. Mol Biol Cell 16:5094–5102. https://doi.org/10.1091/mbc.E05-06-0590

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  115. Fehrenbacher KL, Yang HC, Gay AC et al (2004) Live cell imaging of mitochondrial movement along actin cables in budding yeast. Curr Biol 14:1996–2004. https://doi.org/10.1016/j.cub.2004.11.004

    Article  CAS  PubMed  Google Scholar 

  116. García-Rodríguez LJ, Gay AC, Pon LA (2007) Puf3p, a Pumilio family RNA binding protein, localizes to mitochondria and regulates mitochondrial biogenesis and motility in budding yeast. J Cell Biol 176:197–207. https://doi.org/10.1083/jcb.200606054

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  117. Haraguchi T, Ito K, Duan Z et al (2018) Functional diversity of class XI myosins in Arabidopsis thaliana. Plant Cell Physiol 59:2268–2277. https://doi.org/10.1093/pcp/pcy147

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  118. Peremyslov VV, Prokhnevsky AI, Avisar D, Dolja VV (2008) Two class XI myosins function in organelle trafficking and root hair development in Arabidopsis. Plant Physiol 146:1109–1116. https://doi.org/10.1104/pp.107.113654

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  119. Quintero OA, DiVito MM, Adikes RC et al (2009) Human Myo19 is a novel myosin that associates with mitochondria. Curr Biol 19:2008–2013. https://doi.org/10.1016/j.cub.2009.10.026

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  120. López-Doménech G, Covill-Cooke C, Ivankovic D et al (2018) Miro proteins coordinate microtubule- and actin-dependent mitochondrial transport and distribution. EMBO J 37:321–336. https://doi.org/10.15252/embj.201696380

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  121. Oeding SJ, Majstrowicz K, Hu X-P et al (2018) Identification of Miro1 and Miro2 as mitochondrial receptors for myosin XIX. J Cell Sci. https://doi.org/10.1242/jcs.219469

    Article  PubMed  Google Scholar 

  122. Bocanegra JL, Fujita BM, Melton NR et al (2020) The MyMOMA domain of MYO19 encodes for distinct Miro-dependent and Miro-independent mechanisms of interaction with mitochondrial membranes. Cytoskeleton 77:149–166. https://doi.org/10.1002/cm.21560

    Article  CAS  PubMed  Google Scholar 

  123. Shneyer BI, Ušaj M, Henn A (2016) Myo19 is an outer mitochondrial membrane motor and effector of starvation-induced filopodia. J Cell Sci 129:543–556. https://doi.org/10.1242/jcs.175349

    Article  CAS  PubMed  Google Scholar 

  124. Hawthorne JL, Mehta PR, Singh PP et al (2016) Positively charged residues within the MYO19 MyMOMA domain are essential for proper localization of MYO19 to the mitochondrial outer membrane. Cytoskeleton (Hoboken) 73:286–299. https://doi.org/10.1002/cm.21305

    Article  CAS  Google Scholar 

  125. Rohn JL, Patel JV, Neumann B et al (2014) Myo19 ensures symmetric partitioning of mitochondria and coupling of mitochondrial segregation to cell division. Curr Biol 24:2598–2605. https://doi.org/10.1016/j.cub.2014.09.045

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  126. Kruppa AJ, Kishi-Itakura C, Masters TA et al (2018) Myosin VI-dependent actin cages encapsulate parkin-positive damaged mitochondria. Dev Cell 44:484-499.e6. https://doi.org/10.1016/j.devcel.2018.01.007

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  127. Elhanany-Tamir H, Yu YV, Shnayder M et al (2012) Organelle positioning in muscles requires cooperation between two KASH proteins and microtubules. J Cell Biol 198:833–846. https://doi.org/10.1083/jcb.201204102

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  128. Hedgecock EM, Nichol Thomson J (1982) A gene required for nuclear and mitochondrial attachment in the nematode Caenorhabditis elegans. Cell 30:321–330. https://doi.org/10.1016/0092-8674(82)90038-1

    Article  CAS  PubMed  Google Scholar 

  129. Starr DA, Han M (2002) Role of ANC-1 in tethering nuclei to the actin cytoskeleton. Science 298:406–409. https://doi.org/10.1126/science.1075119

    Article  CAS  PubMed  Google Scholar 

  130. Ono S, Baillie DL, Benian GM (1999) UNC-60B, an ADF/Cofilin family protein, is required for proper assembly of actin into myofibrils in Caenorhabditis elegans body wall muscle. J Cell Biol 145:491–502. https://doi.org/10.1083/jcb.145.3.491

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  131. Schultz J, Lee SJ, Cole T et al (2017) The secreted MSP domain of C. elegans VAPB homolog VPR-1 patterns the adult striated muscle mitochondrial reticulum via SMN-1. J Cell Sci 130:2175–2186. https://doi.org/10.1242/dev.152025

    Article  CAS  Google Scholar 

  132. Russo GJ, Louie K, Wellington A et al (2009) Drosophila Miro is required for both anterograde and retrograde axonal mitochondrial transport. J Neurosci 29:5443–5455. https://doi.org/10.1523/JNEUROSCI.5417-08.2009

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  133. Melkov A, Baskar R, Alcalay Y, Abdu U (2016) A new mode of mitochondrial transport and polarized sorting regulated by Dynein, Milton and Miro. Development 143:4203–4213. https://doi.org/10.1242/dev.138289

    Article  CAS  PubMed  Google Scholar 

  134. Fransson Å, Ruusala A, Aspenström P (2003) Atypical Rho GTPases have roles in mitochondrial homeostasis and apoptosis. J Biol Chem 278:6495–6502. https://doi.org/10.1074/jbc.M208609200

    Article  CAS  PubMed  Google Scholar 

  135. Giot L, Bader JS, Brouwer C et al (2003) A protein interaction map of Drosophila melanogaster. Science 302:1727–1736. https://doi.org/10.1126/science.1090289

    Article  CAS  PubMed  Google Scholar 

  136. Brickley K, Stephenson FA (2011) Trafficking kinesin protein (TRAK)-mediated transport of mitochondria in axons of hippocampal neurons. J Biol Chem 286:18079–18092. https://doi.org/10.1074/jbc.M111.236018

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  137. van Spronsen M, Mikhaylova M, Lipka J et al (2013) TRAK/Milton motor-adaptor proteins steer mitochondrial trafficking to axons and dendrites. Neuron 77:485–502. https://doi.org/10.1016/j.neuron.2012.11.027

    Article  CAS  PubMed  Google Scholar 

  138. Morlino G, Barreiro O, Baixauli F et al (2014) Miro-1 links mitochondria and microtubule dynein motors to control lymphocyte migration and polarity. Mol Cell Biol 34:1412–1426. https://doi.org/10.1128/MCB.01177-13

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  139. Kanfer G, Courthéoux T, Peterka M et al (2015) Mitotic redistribution of the mitochondrial network by Miro and Cenp-F. Nat Commun 6:8015. https://doi.org/10.1038/ncomms9015

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  140. Kanfer G, Peterka M, Arzhanik VK et al (2017) CENP-F couples cargo to growing and shortening microtubule ends. Mol Biol Cell 28:2400–2409. https://doi.org/10.1091/mbc.e16-11-0756

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  141. Peterka M, Kornmann B (2019) Miro-dependent mitochondrial pool of CENP-F and its farnesylated C-terminal domain are dispensable for normal development in mice. PLOS Genet 15:e1008050

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  142. López-Doménech G, Higgs NF, Vaccaro V et al (2016) Loss of dendritic complexity precedes neurodegeneration in a mouse model with disrupted mitochondrial distribution in mature dendrites. Cell Rep 17:317–327. https://doi.org/10.1016/j.celrep.2016.09.004

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  143. Su Q, Cai Q, Gerwin C et al (2004) Syntabulin is a microtubule-associated protein implicated in syntaxin transport in neurons. Nat Cell Biol 6:941–953. https://doi.org/10.1038/ncb1169

    Article  CAS  PubMed  Google Scholar 

  144. Cai Q, Gerwin C, Sheng Z-H (2005) Syntabulin-mediated anterograde transport of mitochondria along neuronal processes. J Cell Biol 170:959–969. https://doi.org/10.1083/jcb.200506042

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  145. Ma H, Cai Q, Lu W et al (2009) KIF5B motor adaptor syntabulin maintains synaptic transmission in sympathetic neurons. J Neurosci 29:13019–13029. https://doi.org/10.1523/JNEUROSCI.2517-09.2009

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  146. Misko A, Jiang S, Wegorzewska I et al (2010) Mitofusin 2 is necessary for transport of axonal mitochondria and interacts with the Miro/Milton complex. J Neurosci 30:4232–4240. https://doi.org/10.1523/JNEUROSCI.6248-09.2010

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  147. Lee CA, Chin L-S, Li L (2018) Hypertonia-linked protein Trak1 functions with mitofusins to promote mitochondrial tethering and fusion. Protein Cell 9:693–716. https://doi.org/10.1007/s13238-017-0469-4

    Article  CAS  PubMed  Google Scholar 

  148. Misgeld T, Kerschensteiner M, Bareyre FM et al (2007) Imaging axonal transport of mitochondria in vivo. Nat Methods 4:559–561. https://doi.org/10.1038/nmeth1055

    Article  CAS  PubMed  Google Scholar 

  149. Kang JS, Tian JH, Pan PY et al (2008) Docking of axonal mitochondria by syntaphilin controls their mobility and affects short-term facilitation. Cell 132:137–148. https://doi.org/10.1016/j.cell.2007.11.024

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  150. Miragoli M, Sanchez-Alonso JL, Bhargava A et al (2016) Microtubule-dependent mitochondria alignment regulates calcium release in response to nanomechanical stimulus in heart myocytes. Cell Rep 14:140–151. https://doi.org/10.1016/j.celrep.2015.12.014

    Article  CAS  PubMed  Google Scholar 

  151. Macaskill AF, Rinholm JE, Twelvetrees AE et al (2009) Miro1 is a calcium sensor for glutamate receptor-dependent localization of mitochondria at synapses. Neuron 61:541–555. https://doi.org/10.1016/j.neuron.2009.01.030

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  152. Stephen T-L, Higgs NF, Sheehan DF et al (2015) Miro1 regulates activity-driven positioning of mitochondria within astrocytic processes apposed to synapses to regulate intracellular calcium signaling. J Neurosci 35:15996–16011. https://doi.org/10.1523/JNEUROSCI.2068-15.2015

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  153. Chen Y, Sheng Z-H (2013) Kinesin-1-syntaphilin coupling mediates activity-dependent regulation of axonal mitochondrial transport. J Cell Biol 202:351–364. https://doi.org/10.1083/jcb.201302040

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  154. Verreet T, Weaver CJ, Hino H et al (2019) Syntaphilin-mediated docking of mitochondria at the growth cone is dispensable for axon elongation in vivo. eNeuro 6:ENEURO.0026-19.2019. https://doi.org/10.1523/ENEURO.0026-19.2019

    Article  PubMed Central  PubMed  Google Scholar 

  155. Ohno N, Chiang H, Mahad DJ et al (2014) Mitochondrial immobilization mediated by syntaphilin facilitates survival of demyelinated axons. Proc Natl Acad Sci 111:9953–9958. https://doi.org/10.1073/pnas.1401155111

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  156. Caino MC, Seo JH, Wang Y et al (2017) Syntaphilin controls a mitochondrial rheostat for proliferation-motility decisions in cancer. J Clin Invest 127:3755–3769. https://doi.org/10.1172/JCI93172

    Article  PubMed Central  PubMed  Google Scholar 

  157. Walch L, Pellier E, Leng W et al (2018) GBF1 and Arf1 interact with miro and regulate mitochondrial positioning within cells. Sci Rep 8:17121. https://doi.org/10.1038/s41598-018-35190-0

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  158. Onodera Y, Nam J-M, Horikawa M et al (2018) Arf6-driven cell invasion is intrinsically linked to TRAK1-mediated mitochondrial anterograde trafficking to avoid oxidative catastrophe. Nat Commun 9:2682. https://doi.org/10.1038/s41467-018-05087-7

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  159. Choi GE, Oh JY, Lee HJ et al (2018) Glucocorticoid-mediated ER-mitochondria contacts reduce AMPA receptor and mitochondria trafficking into cell terminus via microtubule destabilization. Cell Death Dis 9:1137. https://doi.org/10.1038/s41419-018-1172-y

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  160. Hooikaas PJ, Martin M, Mühlethaler T et al (2019) MAP7 family proteins regulate kinesin-1 recruitment and activation. J Cell Biol. https://doi.org/10.1083/jcb.201808065

    Article  PubMed Central  PubMed  Google Scholar 

  161. Pan X, Cao Y, Stucchi R et al (2019) MAP7D2 localizes to the proximal axon and locally promotes kinesin-1-mediated cargo transport into the axon. Cell Rep 26:1988-1999.e6. https://doi.org/10.1016/j.celrep.2019.01.084

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  162. Ebneth A, Godemann R, Stamer K et al (1998) Overexpression of Tau protein inhibits kinesin-dependent trafficking of vesicles, mitochondria, and endoplasmic reticulum: implications for Alzheimer ’s disease. J Cell Biol 143:777–794. https://doi.org/10.1083/jcb.143.3.777

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  163. Ren Y, Zhao J, Feng J (2003) Parkin binds to α/β tubulin and increases their ubiquitination and degradation. J Neurosci 23:3316–3324. https://doi.org/10.1523/JNEUROSCI.23-08-03316.2003

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  164. Yang F, Jiang Q, Zhao J et al (2005) Parkin stabilizes microtubules through strong binding mediated by three independent domains. J Biol Chem 280:17154–17162. https://doi.org/10.1074/jbc.M500843200

    Article  CAS  PubMed  Google Scholar 

  165. Cartelli D, Amadeo A, Calogero AM et al (2018) Parkin absence accelerates microtubule aging in dopaminergic neurons. Neurobiol Aging 61:66–74. https://doi.org/10.1016/j.neurobiolaging.2017.09.010

    Article  CAS  PubMed  Google Scholar 

  166. Vulinovic F, Krajka V, Hausrat TJ et al (2018) Motor protein binding and mitochondrial transport are altered by pathogenic TUBB4A variants. Hum Mutat 39:1901–1915. https://doi.org/10.1002/humu.23602

    Article  CAS  PubMed  Google Scholar 

  167. Stykel MG, Humphries K, Kirby MP et al (2018) Nitration of microtubules blocks axonal mitochondrial transport in a human pluripotent stem cell model of Parkinson’s disease. FASEB J 32:5350–5364. https://doi.org/10.1096/fj.201700759RR

    Article  CAS  PubMed  Google Scholar 

  168. Gilmore-Hall S, Kuo J, Ward JM et al (2019) CCP1 promotes mitochondrial fusion and motility to prevent Purkinje cell neuron loss in pcd mice. J Cell Biol 218:206–219. https://doi.org/10.1083/jcb.201709028

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  169. Magiera MM, Bodakuntla S, Žiak J et al (2018) Excessive tubulin polyglutamylation causes neurodegeneration and perturbs neuronal transport. EMBO J 37:e100440. https://doi.org/10.15252/embj.2018100440

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  170. Bodakuntla S, Schnitzler A, Villablanca C et al (2020) Tubulin polyglutamylation is a general traffic-control mechanism in hippocampal neurons. J Cell Sci 133:jcs241802. https://doi.org/10.1242/jcs.241802

    Article  CAS  PubMed  Google Scholar 

  171. Jackson CL, Bouvet S (2014) Arfs at a Glance. J Cell Sci 127:4103–4109. https://doi.org/10.1242/jcs.144899

    Article  CAS  PubMed  Google Scholar 

  172. Aoki K, Taketo MM (2007) Adenomatous polyposis coli (APC): a multi-functional tumor suppressor gene. J Cell Sci 120:3327–3335. https://doi.org/10.1242/jcs.03485

    Article  CAS  PubMed  Google Scholar 

  173. Pekkurnaz G, Trinidad JC, Wang X et al (2014) Glucose regulates mitochondrial motility via Milton modification by O-GlcNAc transferase. Cell 158:54–68. https://doi.org/10.1016/j.cell.2014.06.007

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  174. Taylor RP, Geisler TS, Chambers JH, McClain DA (2009) Up-regulation of O-GlcNAc transferase with glucose deprivation in HepG2 cells is mediated by decreased hexosamine pathway flux. J Biol Chem 284:3425–3432. https://doi.org/10.1074/jbc.m803198200

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  175. Iyer SPN, Akimoto Y, Hart GW (2003) Identification and cloning of a novel family of coiled-coil domain proteins that interact with O-GlcNAc transferase. J Biol Chem 278:5399–5409. https://doi.org/10.1074/jbc.M209384200

    Article  CAS  PubMed  Google Scholar 

  176. Brickley K, Pozo K, Stephenson FA (2011) N-acetylglucosamine transferase is an integral component of a kinesin-directed mitochondrial trafficking complex. Biochim Biophys Acta 1813:269–281. https://doi.org/10.1016/j.bbamcr.2010.10.011

    Article  CAS  PubMed  Google Scholar 

  177. Wong YC, Ysselstein D, Krainc D (2018) Mitochondria–lysosome contacts regulate mitochondrial fission via RAB7 GTP hydrolysis. Nature 554:382–386. https://doi.org/10.1038/nature25486

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  178. de Brito OM, Scorrano L (2008) Mitofusin 2 tethers endoplasmic reticulum to mitochondria. Nature 456:605–610. https://doi.org/10.1038/nature07534

    Article  CAS  PubMed  Google Scholar 

  179. Schwarz TL (2013) Mitochondrial trafficking in neurons. Cold Spring Harb Perspect Biol 5:a011304–a011304. https://doi.org/10.1101/cshperspect.a011304

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  180. Diokmetzidou A, Soumaka E, Kloukina I et al (2016) Desmin and αB-crystallin interplay in the maintenance of mitochondrial homeostasis and cardiomyocyte survival. J Cell Sci 129:3705–3720. https://doi.org/10.1242/jcs.192203

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  181. Winter L, Wittig I, Peeva V et al (2016) Mutant desmin substantially perturbs mitochondrial morphology, function and maintenance in skeletal muscle tissue. Acta Neuropathol 132:453–473. https://doi.org/10.1007/s00401-016-1592-7

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  182. Hnia K, Tronchère H, Tomczak KK et al (2011) Myotubularin controls desmin intermediate filament architecture and mitochondrial dynamics in human and mouse skeletal muscle. J Clin Invest 121:70–85. https://doi.org/10.1172/JCI44021

    Article  CAS  PubMed  Google Scholar 

  183. Smolina N, Khudiakov A, Knyazeva A et al (2020) Desmin mutations result in mitochondrial dysfunction regardless of their aggregation properties. Biochim Biophys acta Mol basis Dis 1866:165745. https://doi.org/10.1016/j.bbadis.2020.165745

    Article  CAS  PubMed  Google Scholar 

  184. Joubert R, Vignaud A, Le M et al (2013) Site-specific Mtm1 mutagenesis by an AAV-Cre vector reveals that myotubularin is essential in adult muscle. Hum Mol Genet 22:1856–1866. https://doi.org/10.1093/hmg/ddt038

    Article  CAS  PubMed  Google Scholar 

  185. Matveeva EA, Venkova LS, Chernoivanenko IS, Minin AA (2015) Vimentin is involved in regulation of mitochondrial motility and membrane potential by Rac1. Biol Open 4:1290–1297. https://doi.org/10.1242/bio.011874

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  186. Nekrasova OE, Mendez MG, Chernoivanenko IS et al (2011) Vimentin intermediate filaments modulate the motility of mitochondria. Mol Biol Cell 22:2282–2289. https://doi.org/10.1091/mbc.E10-09-0766

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  187. Yardeni T, Fine R, Joshi Y et al (2018) High content image analysis reveals function of miR-124 upstream of Vimentin in regulating motor neuron mitochondria. Sci Rep 8:59. https://doi.org/10.1038/s41598-017-17878-x

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  188. Gentil BJ, Minotti S, Beange M et al (2012) Normal role of the low-molecular-weight neurofilament protein in mitochondrial dynamics and disruption in Charcot-Marie-Tooth disease. FASEB J Off Publ Fed Am Soc Exp Biol 26:1194–1203. https://doi.org/10.1096/fj.11-196345

    Article  CAS  Google Scholar 

  189. Perrot R, Julien J-P (2009) Real-time imaging reveals defects of fast axonal transport induced by disorganization of intermediate filaments. FASEB J 23:3213–3225. https://doi.org/10.1096/fj.09-129585

    Article  CAS  PubMed  Google Scholar 

  190. Israeli E, Dryanovski DI, Schumacker PT et al (2016) Intermediate filament aggregates cause mitochondrial dysmotility and increase energy demands in giant axonal neuropathy. Hum Mol Genet 25:2143–2157. https://doi.org/10.1093/hmg/ddw081

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  191. Rappaport L, Oliviero P, Samuel JL (1998) Cytoskeleton and mitochondrial morphology and function. Mol Cell Biochem 184:101–105

    Article  CAS  PubMed  Google Scholar 

  192. Mandal A, Drerup CM (2019) Axonal transport and mitochondrial function in neurons. Front Cell Neurosci 13:1–11. https://doi.org/10.3389/fncel.2019.00373

    Article  CAS  Google Scholar 

  193. Zhou H, Wang J (2018) BI1 alleviates cardiac microvascular ischemia—reperfusion injury via modifying mitochondrial fission and inhibiting XO/ROS/F - actin pathways. J Cell Physiol. https://doi.org/10.1002/jcp.27308

    Article  PubMed Central  PubMed  Google Scholar 

  194. Spillane M, Ketschek A, Merianda TT et al (2013) Mitochondria coordinate sites of axon branching through localized intra-axonal protein synthesis. Cell Rep 5:1564–1575. https://doi.org/10.1016/j.celrep.2013.11.022.Mitochondria

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  195. Takahashi K, Miura Y, Ohsawa I et al (2018) In vitro rejuvenation of brain mitochondria by the inhibition of actin polymerization. Sci Rep 8:2–11. https://doi.org/10.1038/s41598-018-34006-5

    Article  CAS  Google Scholar 

  196. Sheng Z-H, Cai Q (2012) Mitochondrial transport in neurons: impact on synaptic homeostasis and neurodegeneration. Nat Rev Neurosci 13:77–93. https://doi.org/10.1038/nrn3156

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  197. Aschrafi A, Kar AN, Gale J et al (2016) A heterogeneous population of nuclear-encoded mitochondrial mRNAs is present in the axons of primary sympathetic neurons. Mitochondrion 30:18–23. https://doi.org/10.1016/j.mito.2016.06.002.A

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  198. Pushpalatha KV, Besse F (2019) Local translation in axons: when membraneless RNP granules meet membrane-bound organelles. Front Mol Biosci 6:1–12. https://doi.org/10.3389/fmolb.2019.00129

    Article  CAS  Google Scholar 

  199. Jansen R-P, Niessing D, Baumann S, Feldbrugge M (2014) mRNA transport meets membrane traffic. Trends Genet 30:408–417. https://doi.org/10.1016/j.tig.2014.07.002

    Article  CAS  PubMed  Google Scholar 

  200. Hu J, Chu Z, Han J et al (2014) Phosphorylation-dependent mitochondrial translocation of MAP4 is an early step in hypoxia-induced apoptosis in cardiomyocytes. Cell Death Differ 5:1–11. https://doi.org/10.1038/cddis.2014.369

    Article  CAS  Google Scholar 

  201. Li L, Zhang Q, Zhang X et al (2018) Microtubule associated protein 4 phosphorylation leads to pathological cardiac remodeling in mice. EBioMedicine 37:221–235. https://doi.org/10.1016/j.ebiom.2018.10.017

    Article  PubMed Central  PubMed  Google Scholar 

  202. Li L, Zhang J, Zhang Q et al (2019) Cardiac proteomics reveals the potential mechanism of microtubule associated mitochondrial dysfunction. Burn Trauma 7:1–9

    Google Scholar 

  203. Chu JHZ, Han J (2010) The p38/MAPK pathway regulates microtubule polymerization through phosphorylation of MAP4 and Op18 in hypoxic cells. Cell Mol Life Sci 67:321–333. https://doi.org/10.1007/s00018-009-0187-z

    Article  CAS  PubMed  Google Scholar 

  204. Kitazawa H, Iida J, Uchida A et al (2000) Ser787 in the proline-rich region of human MAP4 is a critical phosphorylation site that reduces its activity to promote tubulin polymerization. Cell Struct Funct 25:33–39

    Article  CAS  PubMed  Google Scholar 

  205. Srsen V, Kitazawa H, Sugita M et al (1999) Serum dependent phosphoryation of human MAP4 at Ser696 in cultured mammalian cells. Cell Struct Funct 24:321–327

    Article  CAS  PubMed  Google Scholar 

  206. Rostovtseva TK, Sheldon KL, Hassanzadeh E et al (2008) Tubulin binding blocks mitochondrial voltage-dependent anion channel and regulates respiration. Proc Natl Acad Sci U S A 105:18746–18751

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  207. Rovini A (2019) Tubulin-VDAC interaction : molecular basis for mitochondrial dysfunction in chemotherapy-induced peripheral neuropathy. Front Physiol 10:1–8. https://doi.org/10.3389/fphys.2019.00671

    Article  Google Scholar 

  208. Prins KW, Humston JL, Mehta A et al (2009) Dystrophin is a microtubule-associated protein. J Cell Biol 186:363–369. https://doi.org/10.1083/jcb.200905048

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  209. Kuznetsov AV, Winkler K, Wiedemann FR et al (1998) Impaired mitochondrial oxidative phosphorylation in skeletal muscle of the dystrophin-deficient mdx mouse. Mol Cell Biochem 183:87–96

    Article  CAS  PubMed  Google Scholar 

  210. Allen DG, Whitehead NP, Froehner SC (2016) Absence of Dystrophin disrupts skeletal muscle signaling: roles of Ca2+, reactive oxygen species, and nitric oxide in the development of muscular dystrophy. Physiol Rev 96:253–305. https://doi.org/10.1152/physrev.00007.2015

    Article  CAS  PubMed  Google Scholar 

  211. Capetanaki Y (2002) Desmin cytoskeleton: a potential regulator of muscle mitochondrial behavior and function. Trends Cardiovasc Med 12:339–348

    Article  CAS  PubMed  Google Scholar 

  212. Milner DJ, Weitzer G, Tran D et al (1996) Disruption of muscle architecture and myocardial degeneration in mice lacking desmin. J Cell Biol 134:1255–1270

    Article  CAS  PubMed  Google Scholar 

  213. Capetanaki Y, Bloch RJ, Kouloumenta A et al (2007) Muscle intermediate filaments and their links to membranes and membranous organelles. Exp Cell Res 3:2063–2076. https://doi.org/10.1016/j.yexcr.2007.03.033

    Article  CAS  Google Scholar 

  214. Milne DJ, Taffet GE, Wang X et al (1999) The absence of desmin leads to cardiomyocyte hypertrophy and cardiac dilation with compromised systolic function. J Mol Cell Cardiol 31:2063–2076

    Article  Google Scholar 

  215. Matveeva EA, Chernoivanenko IS, Minin AA (2010) Vimentin intermediate filaments protect mitochondria from oxidative stress 1. Biochem Suppl Ser A Membr Cell Biol 4:471–481. https://doi.org/10.1134/S199074781004001X

    Article  Google Scholar 

  216. Lehmann SM, Leube RE, Schwarz N (2019) Keratin 6a mutations lead to impaired mitochondrial quality control. Br J Dermatol. https://doi.org/10.1111/bjd.18014

    Article  PubMed  Google Scholar 

  217. Nagashima S, Tábara L-C, Tilokani L et al (2020) Golgi-derived PI(4)P-containing vesicles drive late steps of mitochondrial division. Science 367:1366–1371. https://doi.org/10.1126/science.aax6089

    Article  CAS  PubMed  Google Scholar 

  218. Helle SCJ, Feng Q, Aebersold MJ et al (2017) Mechanical force induces mitochondrial fission. Elife 6:e30292. https://doi.org/10.7554/eLife.30292

    Article  PubMed Central  PubMed  Google Scholar 

  219. Dilsizoglu Senol A, Pepe A, Grudina C et al (2019) Effect of tolytoxin on tunneling nanotube formation and function. Sci Rep 9:5741. https://doi.org/10.1038/s41598-019-42161-6

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  220. Keller KE, Bradley JM, Sun YY et al (2017) Tunneling nanotubes are novel cellular structures that communicate signals between trabecular meshwork cells. Invest Ophthalmol Vis Sci 58:5298–5307. https://doi.org/10.1167/iovs.17-22732

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  221. He K, Shi X, Zhang X et al (2011) Long-distance intercellular connectivity between cardiomyocytes and cardiofibroblasts mediated by membrane nanotubes. Cardiovasc Res 92:39–47. https://doi.org/10.1093/cvr/cvr189

    Article  CAS  PubMed  Google Scholar 

  222. Burt R, Dey A, Aref S et al (2019) Activated stromal cells transfer mitochondria to rescue acute lymphoblastic leukemia cells from oxidative stress. Blood 134:1415–1429. https://doi.org/10.1182/blood.2019001398

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  223. Dubey J, Ratnakaran N, Koushika SP (2015) Neurodegeneration and microtubule dynamics: death by a thousand cuts. Front Cell Neurosci 9:1–15. https://doi.org/10.3389/fncel.2015.00343

    Article  CAS  Google Scholar 

  224. Sequeira V, Nijenkamp LLAM, Regan JA, Van Der Velden J (2014) The physiological role of cardiac cytoskeleton and its alterations in heart failure. Biochim Biophys Acta 1838:700–722. https://doi.org/10.1016/j.bbamem.2013.07.011

    Article  CAS  PubMed  Google Scholar 

  225. Clarkson E, Costa CF, Machesky LM (2004) Congenital myopathies: diseases of the actin cytoskeleton. J Pathol 204:407–417. https://doi.org/10.1002/path.1648

    Article  CAS  PubMed  Google Scholar 

  226. Wang Y, Xu E, Musich PR, Lin F (2019) Mitochondrial dysfunction in neurodegenerative diseases and the potential countermeasure. CNS Neurosci Ther 25:816–824. https://doi.org/10.1111/cns.13116

    Article  PubMed Central  PubMed  Google Scholar 

  227. Siasos G, Tsigkou V, Kosmopoulos M et al (2018) Mitochondria and cardiovascular diseases—from pathophysiology to treatment. Ann Transl Med 6:256. https://doi.org/10.21037/atm.2018.06.21

    Article  CAS  PubMed Central  PubMed  Google Scholar 

Download references

Acknowledgements

We thank N. A. Tirumala and H. Kumar for constructive comments on the manuscript.

Funding

VA was supported by extramural funding from the Welcome Trust/Department of Biotechnology–India Alliance (grant IA/18/1/503607), the Women Excellence Award from the Science and Engineering Research Board, India, intramural funding from the Indian Institute of Science, and the RI Mazumdar Young Investigator Award.

Author information

Author notes

  1. Vaishnavi Ananthanarayanan

    Present address: EMBL Australia Node in Single Molecule Science, School of Medical Sciences, University of New South Wales, Sydney, Australia

Authors and Affiliations

  1. Centre for BioSystems Science and Engineering, Indian Institute of Science, Bangalore, India

    Mitali Shah, Leeba Ann Chacko, Joel P. Joseph & Vaishnavi Ananthanarayanan

Authors
  1. Mitali Shah
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Leeba Ann Chacko
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Joel P. Joseph
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Vaishnavi Ananthanarayanan
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Vaishnavi Ananthanarayanan.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest with the contents of this article.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Shah, M., Chacko, L.A., Joseph, J.P. et al. Mitochondrial dynamics, positioning and function mediated by cytoskeletal interactions. Cell. Mol. Life Sci. 78, 3969–3986 (2021). https://doi.org/10.1007/s00018-021-03762-5

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00018-021-03762-5

Keywords

Search

Navigation