Skip to main content
SpringerLink
Log in
Book cover

Biochemistry of Oxidative Stress pp 95–108Cite as

Mitochondrial Transfer by Intercellular Nanotubes

  • Chapter
  • First Online:

  • 1639 Accesses

Part of the book series: Advances in Biochemistry in Health and Disease ((ABHD,volume 16))

Abstract

Cell-to-cell communication is a critical requirement for the coordination of cell behavior in tissue homeostasis and the conservation of multicellular organisms. Among several types of intercellular communication, tunneling nanotubes (TNTs) were discovered no more than a decade ago but are now known to constitute intercellular bridges connecting distant cells. Over the last decade, research has shown TNTs to have structural and functional properties which vary across cell types. TNTs permit cell-to-cell communication on the basis of membrane continuity between connected cells and are capable of transferring various types of intracellular components including calcium ions, cytoplasmic molecules and different types of organelles. In this chapter, we will describe the different mechanisms of TNT formation, their heterogeneous composition and their functional roles in physiological and pathological processes. In this context, we also discuss the importance of mitochondria transfer from stem cells to recipient cells with nonfunctional mitochondria, which results in a significant improvement in aerobic respiration. The transfer of healthy mitochondria through TNTs may rescue damaged cells and thus constitute an alternative therapeutic approach for pathologies involving oxidative stress.

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

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   149.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   199.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   199.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

References

  1. Kumar N, Gilula NB (1996) The gap junction communication channel. Cell 84:381–388

    Article  CAS  PubMed  Google Scholar 

  2. Denzer K, Kleijmeer MJ, Heijnen HF et al (2000) Exosome: from internal vesicle of the multivesicular body to intercellular signaling device. J Cell Sci 19:3365–3374

    Google Scholar 

  3. Ramirez-Weber FA, Kornberg TB (2000) Signaling reaches to new dimensions in Drosophila imaginal discs. Cell 103:189–192

    Article  CAS  PubMed  Google Scholar 

  4. Rustom A, Saffrich R, Markovic I et al (2004) Nanotubular highways for intercellular organelle transport. Science 303:1007–1010

    Article  CAS  PubMed  Google Scholar 

  5. Gerdes H-H, Bukoreshtliev NV, Barroso JF (2007) Tunneling nanotubes: a new route for the exchange of components between animal cells. FEBS Lett 581:2194–2201

    Article  CAS  PubMed  Google Scholar 

  6. Chinnery HR, Pearlman E, Mc Menamin PG (2008) Cutting edge: membrane nanotubes in vivo. A feature of MHC class II+ cells in the mouse cornea. J Immunol 180:5779–5783

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Gerdes H-H, Rustom A, Wang X (2013) Tunneling nanotubes, an emerging intercellular communication route in development. Mech Develop 130:381–387

    Article  CAS  Google Scholar 

  8. Seyed-Razavi Y, Hickey MJ, Zuffová L et al (2013) Membrane nanotubes in myeloid cells in adult mouse cornea represent a novel mode of immune cells interaction. Immunol Cell Biol 91:89–95

    Article  CAS  PubMed  Google Scholar 

  9. Lou E, Fujisawa S, Barlas A et al (2012) Tunneling nanotubes: a new paradigm for studying intercellular communication and therapeutics in cancer. Commun Integr Biol 5:399–403

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Astanina K, Koch M, Jüngst C et al (2015) Lipid droplets as a novel cargo to tunneling nanotubes in endotelial cells. Sci Rep 5:11453. doi:10.1038/srep11453

    Article  PubMed  PubMed Central  Google Scholar 

  11. Sowinski S, Jolly C, Berninghausen O et al (2008) Membrane nanotubes physically connect T cells over long distances presenting a novel route for HIV-1 transmission. Nat Cell Biol 10:211–219

    Article  CAS  PubMed  Google Scholar 

  12. Abounit S, Zurzolo C (2012) Wiring through tunneling nanotubes: from electrical signals to organelle transfer. J Cell Sci 125:1089–1098

    Article  CAS  PubMed  Google Scholar 

  13. Lokar M, Iglic A, Veranic P (2010) Protruding membrane nanotubes: attachment of tubular protrusions to adjacent cells by several anchoring junctions. Protoplasma 246:81–87

    Article  PubMed  Google Scholar 

  14. Önfelt B, Hedvetzki S, Benninger RKP et al (2006) Structurally distinct membrane nanotubes between human macrophages support long-distance vesicular traffic or surfing of bacteria. J Immunol 177:8476–8483

    Article  PubMed  Google Scholar 

  15. Schiller C, Diakopoulos KN, Rohwedder I et al (2013) LST1 promotes the assembly of a molecular machinery responsible for tunneling nanotube formation. J Cell Sci 126:767–777

    Article  CAS  PubMed  Google Scholar 

  16. Smith IF, Shuai J, Parker I (2011) Active generation and propagation of Ca2+ signals within tunneling membrane nanotubes. Biophys J 100:L37–L39

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Watkins SC, Salter RD (2005) Functional connectivity between immune cells mediated by tunneling nanotubes. Immunity 23:309–318

    Article  CAS  PubMed  Google Scholar 

  18. Koyanagi M, Brandes RP, Haendeler J et al (2005) Cell-to-cell connection of endothelial progenitor cells with cardiac myocytes by nanotubes: a novel mechanism for cell fate changes? Circ Res 96:1039–1041

    Article  CAS  PubMed  Google Scholar 

  19. Bernardo ME, Locatelli F, Fibbe WE (2009) Mesenchymal stromal cells. Ann NY Acad Sci 1176:101–117

    Article  CAS  PubMed  Google Scholar 

  20. Takahashi K, Yamanaka S (2006) Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126:663–676

    Article  CAS  PubMed  Google Scholar 

  21. Maherali N, Sridharan R, Xie W et al (2007) Directly reprogrammed fibroblasts show global epigenetic remodeling and widespread tissue contribution. Cell Stem Cell 1:55–70

    Article  CAS  PubMed  Google Scholar 

  22. Freund D, Bauer N, Boxberger S et al (2006) Polarization of human hematopoietic progenitors during contact with multipotent mesenchymal stromal cells: effects on proliferation and clonogenicity. Stem Cell Dev 15:815–829

    Article  CAS  Google Scholar 

  23. Wang Y, Cui J, Sun X, Zhang Y (2011) Tunneling-nanotube development in astrocytes depends on p53 activation. Cell Death Differ 18:732–742

    Article  CAS  PubMed  Google Scholar 

  24. Ding X, Ma M, Teng J et al (2015) Exposure to ALS-FTD-CSF generates TDP-43 aggregates in glioblastoma cells through exosomes and TNTs-like structure. Oncotarget 6:24178–24191

    Article  PubMed  PubMed Central  Google Scholar 

  25. Polak R, de Rooij B, Pieters R et al (2015) B-cell precursor acute lymphoblastic leukemia cells use tunneling nanotubes to orchestrate their microenvironment. Blood 126:2404–2414

    Article  CAS  PubMed  Google Scholar 

  26. Chauveau A, Aucher A, Eissmann P et al (2010) Membrane nanotubes facilitate long-distance interactions between natural killer cells and target cells. Proc Natl Acad Sci U S A 107:5545–5550

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Vidulescu C, Clejan S, O’Connor KC, (2004) Vesicle traffic through intercellular bridges in human prostate cancer cells. J Cell Mol Med 8:388–396

    Article  PubMed  Google Scholar 

  28. Pasquier J, Guerrouahen BS, Al Thawadi H et al (2013) Preferential transfer of mitochondria from endothelialto cancer cells through tunneling nanotubes modulates chemoresistance. J Transl Med 10:11:94

    Google Scholar 

  29. Thayanithy V, Dickson EL, Steer C et al (2014) Tumor-stromal cross talk: direct cell-to-cell transfer of oncogenic microRNAs via tunneling nanotubes. Transl Res 164:359–365

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Dvash E, Rubistein M. (2016) A surprising mediator of oxidative DNA damage. Cell Cycle doi:10.1080/15384101.2016.1144989

    Google Scholar 

  31. Andreazza AC, Wang J-F, Salmasi F et al (2013) Specific subcellular changes in oxidative stress in prefrontal cortex from patients with bipolar disorder. J Neurochem 127:555–561

    Article  Google Scholar 

  32. Ortiz GG, Pacheco-Moisés FP, Bitzer-Quintero OK et al (2013) Immnology and oxidative stress in multiple sclerosis: clinical and basic approach. Clin Devel Immunol 708659. http://dx.doi.org/10.1155/2013/708659

  33. Mir F, Lee D, Ray H, Sadiq SA (2014) CSF isoprostane levels are a biomarker of oxidative stress in multiple sclerosis. Neurol Neuroimmunol Neuroinflamation 1:21. doi:10.1212/NXI.0000000000000021

    Article  Google Scholar 

  34. Engel P (2014) Does metabolic failure at the synapse cause Alzheimer’s disease? Med Hypoth 83:802–808

    Article  CAS  Google Scholar 

  35. Ma Y, Bai RK, Trieu R, Wong LJ (2010) Mitochondrial dysfunction in human breast cancer cells and their transmitochondrial cybrids. Biochim Biophys Acta 1797:29–37

    Article  CAS  PubMed  Google Scholar 

  36. Ernster L (1993) Lipid peroxidation in biological membranes: Mechanisms and implications. In: Yagi K (ed) Active Oxygen, Lipid Peroxides and Antioxidants. CRC Press, Boca Raton, pp 1–38

    Google Scholar 

  37. Lenaz G, Bovian C, Formiggini G et al (1999) Mitochondria, oxidative stress, and Antioxidant defences. Acta Biochim Polonica 46:1–21

    CAS  Google Scholar 

  38. Kaipparettu BA, Ma Y, Park JH et al (2013) Crosstalk from non-cancerous mitochondria can inhibit tumor properties of metastatic cells by suppressing oncogenic pathways. PLoS One 8:e61747. doi:10.1371/journal.pone.0061747

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Spees JL, Olson SD, Whitney MJ et al (2006) Mitochondrial transfer among cells can rescue aerobic respiration. Proc Natl Acad Sci U S A 103:1283–1288

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Domhan S, Ma L, Tai A et al (2011) Intercellular communication by exchange of cytoplasamic material via tunneling nantotube like estructures in primary human renal epithelial cells. PLoS One 6:e21283. doi:10.1371/journal.pone.0021283

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Liu K, Ji K, Guo L et al (2014) Mesenchymal stem cells rescue injured endothelial cells in an in vitro ischemia–reperfusion model via tunneling nanotube like structure mediated mitochondrial transfer. Microvasc Res 92:10–18

    Article  CAS  PubMed  Google Scholar 

  42. Han H, Hu J, Yan Q et al (2016) Bone marrow-derived mesenchymal stem cells rescue injured H9c2 cells via transferring intact mitochondria through tunneling nanotubes in an in vitro simulated ischemia/reperfusion model. Molec Med Rep 13:1517–1524

    CAS  Google Scholar 

  43. Kadiu I, Gendelman H (2011) Human immunodeficiency virus type 1 endocytic trafficking through macrophage bridging conduits facilitates spread of infection. J Neuroimmune Pharmacol 6:658–675

    Article  PubMed  PubMed Central  Google Scholar 

  44. Arkwright P, Luchetti F, Tour J et al (2010) Fas stimulation of T-lymphocytes promotes rapid intercellular exchange of death signals via membrane nanotubes. Cell Res 20:72–88

    Article  CAS  PubMed  Google Scholar 

  45. Gousset K, Schiff E, Langevin C et al (2009) Prions hijack tunneling nanotubes for intercellular spread. Nat Cell Biol 11:328–336

    Article  CAS  PubMed  Google Scholar 

  46. Wang X, Veruki M, Bukoreshtliev N et al (2010) Animal cells connected by nanotubes can be electrically coupled through interposed gap-junction channels. Proc Natl Acad Sci U S A 107:17194–17199

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Cselenyak A, Pankotai E, Horvath EM et al (2010) Mesenchymal stem cells rescue cardiomyoblasts from cell death in an in vitro ischemia model via direct cell-to-cell connections. BMC Cell Biol 20:11–29

    Google Scholar 

  48. Plotnikov EY, Khryapenkov TG, Galkina SI et al (2010) Cytoplasm and organelle transfer between mesenchymal multipotent stromal cells and renal tubular cells in coculture. Exp. Cell Res 316:2447–2455

    Article  CAS  Google Scholar 

  49. Mi L, Xiong R, Zhang Y (2011) Microscopic observation of the intercellular transport of cdte quantum dot aggregates through tunneling-nanotubes. J Biomater Nanobiotechnol 2:173–180

    Article  CAS  Google Scholar 

  50. 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

    Article  CAS  PubMed  Google Scholar 

  51. Acquistapace A, Bru T, Lesault PF et al (2011) Human mesenchymal stem cells reprogram adult cardiomyocytes toward a progenitor-like state through partial cell fusion and mitochondrial transfer. Stem Cells 29:812–824

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Yasuda K, Khandare A, Burianovsky L et al (2011) Tunneling nanotubes mediate rescue of prematurely senescent endothelial cells by endothelial progenitors: exchange of lysosomal pool. Aging 3:597–608

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Lou E, Fujisawa S, Morozov A et al (2012) Tunneling nanotubes provide a unique conduit for intercellular transfer of cellular contents in human malignant pleural mesothelioma. PLoS One 7:e33093

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Wang X, Bukoreshtliev NV, Gerdes HH (2012) Developing neurons form transient nanotubes facilitating electrical coupling and calcium signaling with distant astrocytes. PLoS One 7:e47429

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Bénard M, Schapman D, Lebon A et al (2015) Structural and functional analysis of tunneling nanotubes using CW STED and gconfocal approaches. Biol Cell 107:419–425

    Article  PubMed  Google Scholar 

  56. Naphade S, Sharma J, Gaide-Chevronnay HP et al (2015) Brief reports: lysosomal cross-correction by hematopoietic stem cell-derived macrophages via tunneling nanotubes. Stem Cells 33:301–309

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

The authors would like to thank Dr. N. Villalba, Dr. L. Fiore, Dr. R.J. Gelpi, Dr. A. Boveris and Dr. J.J. Poderoso for authorizing the use of photomicrographs obtained in ongoing collaborative work.

Author information

Authors and Affiliations

  1. Institute of Cell Biology and Neuroscience (UBA-CONICET), School of Medicine, University of Buenos Aires, Buenos Aires, Argentina

    Viviana Sanchez & Alicia Brusco

Authors
  1. Viviana Sanchez
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Alicia Brusco
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Viviana Sanchez .

Editor information

Editors and Affiliations

  1. School of Medicine, University of Buenos Aires, Buenos Aires, Argentina

    Ricardo Jorge Gelpi

  2. School of Pharmacy and Biochemistry, University of Buenos Aires, Buenos Aires, Argentina

    Alberto Boveris

  3. Instituto de Inmunología, Genética y Metabolismo (INIGEM, UBA–CONICET), Laboratorio de Metabolismo del Oxígeno, Hospital Universitario, Universidad de Buenos Aires, Buenos Aires, Argentina

    Juan José Poderoso

Rights and permissions

Reprints and permissions

Copyright information

© 2016 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Sanchez, V., Brusco, A. (2016). Mitochondrial Transfer by Intercellular Nanotubes. In: Gelpi, R., Boveris, A., Poderoso, J. (eds) Biochemistry of Oxidative Stress. Advances in Biochemistry in Health and Disease, vol 16. Springer, Cham. https://doi.org/10.1007/978-3-319-45865-6_7

Download citation

Publish with us

Policies and ethics

Search

Navigation