Journal of Inherited Metabolic Disease

, Volume 32, Issue 2, pp 163–180 | Cite as

Organelle dynamics and dysfunction: A closer link between peroxisomes and mitochondria

  • F. Camões
  • N. A. Bonekamp
  • H. K. Delille
  • M. Schrader
SSIEM Symposium 2008


Mitochondria and peroxisomes are ubiquitous subcellular organelles, which fulfil an indispensable role in the cellular metabolism of higher eukaryotes. Moreover, they are highly dynamic and display large plasticity. There is growing evidence now that both organelles exhibit a closer interrelationship than previously appreciated. This connection includes metabolic cooperations and cross-talk, a novel putative mitochondria-to-peroxisome vesicular trafficking pathway, as well as an overlap in key components of their fission machinery. Thus, peroxisomal alterations in metabolism, biogenesis, dynamics and proliferation can potentially influence mitochondrial functions, and vice versa. In this review, we present the latest progress in the emerging field of peroxisomal and mitochondrial interrelationship with a particular emphasis on organelle dynamics and its implication in diseases.


Mitochondrial Fission Mitochondrial Dynamic Mitochondrial Fusion Division Machinery Cerotic Acid 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



dynamin-like protein


endoplasmic reticulum


mitochondria-derived vesicle


mitochondrial inner membrane


mitochondrial outer membrane


mitochondrial outer membrane permeabilization


mitochondrial DNA


peroxisome biogenesis disorder




peroxisomal membrane protein


peroxisomal targeting signal


reactive oxygen species


small ubiquitin-like modifier




transmembrane domain


very long-chain fatty acids



We apologize to those whose work has not been cited owing to space limitations. This work was supported by the German Research Foundation (DFG; SCHR 518/6–1, 2), the Portuguese Foundation for Science and Technology (FCT; PTDC/BIA–BCM/71932/2006, SFRH/BD/37647/2007 to N.A.B.), and the University of Aveiro.


  1. Achleitner G, Gaigg B, Krasser A, et al (1999) Association between the endoplasmic reticulum and mitochondria of yeast facilitates interorganelle transport of phospholipids through membrane contact. Eur J Biochem 264: 545–553. doi:10.1046/j.1432-1327.1999.00658.x.PubMedGoogle Scholar
  2. Antonenkov VD, Hiltunen JK (2006) Peroxisomal membrane permeability and solute transfer. Biochim Biophys Acta 1763: 1697–1706. doi:10.1016/j.bbamcr.2006.08.044.PubMedGoogle Scholar
  3. Arnoult D, Rismanchi N, Grodet A, et al (2005) Bax/Bak-dependent release of DDP/TIMM8a promotes Drp1-mediated mitochondrial fission and mitoptosis during programmed cell death. Curr Biol 15: 2112–2118. doi:10.1016/j.cub.2005.10.041.PubMedGoogle Scholar
  4. Bach D, Pich S, Soriano FX, et al (2003) Mitofusin–2 determines mitochondrial network architecture and mitochondrial metabolism. A novel regulatory mechanism altered in obesity. J Biol Chem 278: 17190–17197. doi:10.1074/jbc.M212754200.PubMedGoogle Scholar
  5. Barsoum MJ, Yuan H, Gerencser AA, et al (2006) Nitric oxide-induced mitochondrial fission is regulated by dynamin-related GTPases in neurons. EMBOEMBO J 25: 3900–3911. doi:10.1038/sj.emboj.7601253.Google Scholar
  6. Baumgart E, Vanhorebeek I, Grabenbauer M, et al (2001) Mitochondrial alterations caused by defective peroxisomal biogenesis in a mouse model for Zellweger syndrome (PEX5 knockout mouse). Am J Pathol 159: 1477–1494.PubMedGoogle Scholar
  7. Beal MF (2005) Mitochondria take center stage in aging and neurodegeneration. Ann Neurol 58: 495–505. doi:10.1002/ana.20624.PubMedGoogle Scholar
  8. Bereiter-Hahn J, Voth M, Mai S, Jendrach M (2008) Structural implications of mitochondrial dynamics. Biotechnol J 3: 765–780. doi:10.1002/biot.200800024.PubMedGoogle Scholar
  9. Borgese N, Colombo S, Pedrazzini E (2003) The tale of tail-anchored proteins: coming from the cytosol and looking for a membrane. J Cell Biol 161: 1013–1019. doi:10.1083/jcb.200303069.PubMedGoogle Scholar
  10. Borgese N, Brambillasca S, Colombo S (2007) How tails guide tail-anchored proteins to their destinations. Curr Opin Cell Biol 19: 368–375. doi:10.1016/ Scholar
  11. Brooks C, Wei Q, Feng L, et al (2007) Bak regulates mitochondrial morphology and pathology during apoptosis by interacting with mitofusins. Proc Natl Acad Sci U S A 104: 11649–11654. doi:10.1073/pnas.0703976104.PubMedGoogle Scholar
  12. Brosius U, Gartner J (2002) Cellular and molecular aspects of Zellweger syndrome and other peroxisome biogenesis disorders. Cell Mol Life Sci 59: 1058–61069. doi:10.1007/s00018-002-8486-7.PubMedGoogle Scholar
  13. Brown LA, Baker A (2008) Shuttles and cycles: transport of proteins into the peroxisome matrix [Review]. Mol Membr Biol 25: 363–375. doi:10.1080/09687680802130583.PubMedGoogle Scholar
  14. Butow RA, Avadhani NG (2004) Mitochondrial signaling: the retrograde response. Mol Cell 14: 1–15. doi:10.1016/S1097-2765(04)00179-0.PubMedGoogle Scholar
  15. Campello S, Lacalle RA, Bettella M, Manes S, Scorrano L, Viola A (2006) Orchestration of lymphocyte chemotaxis by mitochondrial dynamics. J Exp Med 203: 2879–2886. doi:10.1084/jem.20061877.PubMedGoogle Scholar
  16. Chan DC (2006) Mitochondria: dynamic organelles in disease, aging, and development. Cell 125: 1241–1252. doi:10.1016/j.cell.2006.06.010.PubMedGoogle Scholar
  17. Chandra NC, Spiro MJ, Spiro RG (1998) Identification of a glycoprotein from rat liver mitochondrial inner membrane and demonstration of its origin in the endoplasmic reticulum. J Biol Chem 273: 19715–19721. doi:10.1074/jbc.273.31.19715.PubMedGoogle Scholar
  18. Chang DT, Honick AS, Reynolds IJ (2006) Mitochondrial trafficking to synapses in cultured primary cortical neurons. J Neurosci 26: 7035–7045. doi:10.1523/JNEUROSCI.1012-06.2006.PubMedGoogle Scholar
  19. Chen H, Chan DC (2005) Emerging functions of mammalian mitochondrial fusion and fission. Hum Mol Genet 14: R283–R289. doi:10.1093/hmg/ddi270.PubMedGoogle Scholar
  20. Chen H, Detmer SA, Ewald AJ, Griffin EE, Fraser SE, Chan DC (2003) Mitofusins Mfn1 and Mfn2 coordinately regulate mitochondrial fusion and are essential for embryonic development. J Cell Biol 160: 189–200. doi:10.1083/jcb.200211046.PubMedGoogle Scholar
  21. Cribbs JT, Strack S (2007) Reversible phosphorylation of Drp1 by cyclic AMP-dependent protein kinase and calcineurin regulates mitochondrial fission and cell death. EMBO Rep 8: 939–944. doi:10.1038/sj.embor.7401062.PubMedGoogle Scholar
  22. Delille HK, Schrader M (2008) Targeting of hFis1 to peroxisomes is mediated by Pex19p. J Biol Chem 283: 31107–31115.PubMedGoogle Scholar
  23. Desai M, Hu J (2008) Light induces peroxisome proliferation in Arabidopsis seedlings through the photoreceptor phytochrome A, the transcription factor HY5 HOMOLOG, and the peroxisomal protein PEROXIN11b. Plant Physiol 146: 1117–1127. doi:10.1104/pp.107.113555.PubMedGoogle Scholar
  24. Detmer SA, Chan DC (2007) Functions and dysfunctions of mitochondrial dynamics. Nat Rev Mol Cell Biol 8: 870–879. doi:10.1038/nrm2275.PubMedGoogle Scholar
  25. DiMauro S (2004) Mitochondrial diseases. Biochim Biophys Acta 1658: 80–88. doi:10.1016/j.bbabio.2004.03.014.PubMedGoogle Scholar
  26. Dimauro S, Davidzon G (2005) Mitochondrial DNA and disease. Ann Med 37: 222–232. doi:10.1080/07853890510007368.PubMedGoogle Scholar
  27. DiMauro S, Schon EA (2003) Mitochondrial respiratory-chain diseases. N Engl J Med 348: 2656–2668. doi:10.1056/NEJMra022567.PubMedGoogle Scholar
  28. Dirkx R, Vanhorebeek I, Martens K, et al (2005) Absence of peroxisomes in mouse hepatocytes causes mitochondrial and ER abnormalities. Hepatology 41: 868–878. doi:10.1002/hep.20628.PubMedGoogle Scholar
  29. Elgersma Y, Kwast L, van den Berg M, et al (1997) Overexpression of Pex15p, a phosphorylated peroxisomal integral membrane protein required for peroxisome assembly in S.cerevisiae, causes proliferation of the endoplasmic reticulum membrane. EMBO J 16: 7326–7341. doi:10.1093/emboj/16.24.7326.PubMedGoogle Scholar
  30. Elmore SP, Qian T, Grissom SF, Lemasters JJ (2001) The mitochondrial permeability transition initiates autophagy in rat hepatocytes. FASEB J 15: 2286–2287.PubMedGoogle Scholar
  31. Epstein CB, Waddle JA, Hale W 4th, et al (2001) Genome-wide responses to mitochondrial dysfunction. Mol Biol Cell 12: 297–308.PubMedGoogle Scholar
  32. Erdmann R, Schliebs W (2005) Opinion: peroxisomal matrix protein import: the transient pore model. Nat Rev Mol Cell Biol 6: 738–742. doi:10.1038/nrm1710.PubMedGoogle Scholar
  33. Fagarasanu A, Fagarasanu M, Rachubinski RA (2007) Maintaining peroxisome populations: a story of division and inheritance. Annu Rev Cell Dev Biol 23: 321–344. doi:10.1146/annurev.cellbio.23.090506.123456.PubMedGoogle Scholar
  34. Fan CY, Pan J, Usuda N, Yeldandi AV, Rao MS, Reddy JK (1998) Steatohepatitis, spontaneous peroxisome proliferation and liver tumors in mice lacking peroxisomal fatty acyl-CoA oxidase. Implications for peroxisome proliferator-activated receptor alpha natural ligand metabolism. J Biol Chem 273: 15639–15645. doi:10.1074/jbc.273.25.15639.PubMedGoogle Scholar
  35. Faust PL, Banka D, Siriratsivawong R, Ng VG, Wikander TM (2005) Peroxisome biogenesis disorders: the role of peroxisomes and metabolic dysfunction in developing brain. JInherit Metab Dis 28: 369–383. doi:10.1007/s10545-005-7059-y.PubMedGoogle Scholar
  36. Ferrer I, Kapfhammer J, Hindelang C, et al (2005) Inactivation of the peroxisomal ABCD2 transporter in the mouse leads to late-onset ataxia involving mitochondria, Golgi and endoplasmatic reticulum damage. Hum Mol Genet 14: 3565–3577. doi:10.1093/hmg/ddi384.PubMedGoogle Scholar
  37. Fujiki Y, Matsuzono Y, Matsuzaki T, Fransen M (2006) Import of peroxisomal membrane proteins: the interplay of Pex3p- and Pex19p-mediated interactions. Biochim Biophys Acta 1763: 1639–1646. doi:10.1016/j.bbamcr.2006.09.030.PubMedGoogle Scholar
  38. Gabaldon T, Snel B, van Zimmeren F, Hemrika W, Tabak H, Huynen MA (2006) Origin and evolution of the peroxisomal proteome. Biol Direct 1: 8. doi:10.1186/1745-6150-1-8.PubMedGoogle Scholar
  39. Gandre-Babbe S, van der Bliek AM (2008) The novel tail-anchored membrane protein Mff controls mitochondrial and peroxisomal fission in mammalian cells. Mol Biol Cell 19: 2402–2412. doi:10.1091/mbc.E07-12-1287.PubMedGoogle Scholar
  40. Goglia F, Liverini G, Lanni A, Iossa S, Barletta A (1989) Morphological and functional modifications of rat liver peroxisomal subpopulations during cold exposure. Exp Biol 48: 127–133.PubMedGoogle Scholar
  41. Gomes LC, Scorrano L (2008) High levels of Fis1, a pro-fission mitochondrial protein, trigger autophagy. Biochim Biophys Acta 1777: 860–866. doi:10.1016/j.bbabio.2008.05.442.PubMedGoogle Scholar
  42. Gorgas K (1987) Morphogenesis of peroxisomes in lipid synthesizing epithelia. In: Fahimi HD, Sies H, eds. Peroxisomes in Biology and Medecine. Berlin, Heidelberg: Springer-Verlag, 3–17.Google Scholar
  43. Gould SJ, Collins CS (2002) Opinion: peroxisomal-protein import: is it really that complex? Nat Rev Mol Cell Biol 3: 382–389. doi:10.1038/nrm807.PubMedGoogle Scholar
  44. Grou CP, Carvalho AF, Pinto MP, et al (2008) The peroxisomal protein import machinery—a case report of transient ubiquitination with a new flavor. Cell Mol Life Sci [Sep. 23, Epub ahead of print].Google Scholar
  45. Guo X, Macleod GT, Wellington A, et al (2005) The GTPase dMiro is required for axonal transport of mitochondria to Drosophila synapses. Neuron 47: 379–393. doi:10.1016/j.neuron.2005.06.027.PubMedGoogle Scholar
  46. Haan GJ, Baerends RJ, Krikken AM, Otzen M, Veenhuis M, Klei IJ (2006) Reassembly of peroxisomes in Hansenula polymorpha pex3 cells on reintroduction of Pex3p involves the nuclear envelope. FEMS Yeast Res 6: 186–194. doi:10.1111/j.1567-1364.2006.00037.x.PubMedGoogle Scholar
  47. Halbach A, Landgraf C, Lorenzen S, et al (2006) Targeting of the tail-anchored peroxisomal membrane proteins PEX26 and PEX15 occurs through C-terminal PEX19-binding sites. J Cell Sci 119: 2508–2517. doi:10.1242/jcs.02979.PubMedGoogle Scholar
  48. Harder Z, Zunino R, McBride H (2004) Sumo1 conjugates mitochondrial substrates and participates in mitochondrial fission. Curr Biol 14: 340–345.PubMedGoogle Scholar
  49. Heiland I, Erdmann R (2005) Biogenesis of peroxisomes. Topogenesis of the peroxisomal membrane and matrix proteins. FEBS J 272: 2362–2372. doi:10.1111/j.1742-4658.2005.04690.x.PubMedGoogle Scholar
  50. Herzig S, Martinou JC (2008) Mitochondrial dynamics: to be in good shape to survive. Curr Mol Med 8: 131–137. doi:10.2174/156652408783769625.PubMedGoogle Scholar
  51. Hoepfner D, Schildknegt D, Braakman I, Philippsen P, Tabak HF (2005) Contribution of the endoplasmic reticulum to peroxisome formation. Cell 122: 85–95. doi:10.1016/j.cell.2005.04.025.PubMedGoogle Scholar
  52. Hoivik DJ, Qualls CW Jr, Mirabile RC, et al (2004) Fibrates induce hepatic peroxisome and mitochondrial proliferation without overt evidence of cellular proliferation and oxidative stress in cynomolgus monkeys. Carcinogenesis 25: 1757–1769. Epub 2004 May 6. doi:10.1093/carcin/bgh182.PubMedGoogle Scholar
  53. Hoppins S, Lackner L, Nunnari J (2007) The machines that divide and fuse mitochondria. Annu Rev Biochem 76: 751–780. doi:10.1146/annurev.biochem.76.071905.090048.PubMedGoogle Scholar
  54. Hu J (2007) Plant peroxisome multiplication: highly regulated and still enigmatic. J Integr Plant Biol 49: 1112–1118. doi:10.1111/j.1672-9072.2007.00537.x.Google Scholar
  55. Hulshagen L, Krysko O, Bottelbergs A, et al (2008) Absence of functional peroxisomes from mouse CNS causes dysmyelination and axon degeneration. J Neurosci 28: 4015–4027. doi:10.1523/JNEUROSCI.4968-07.2008.PubMedGoogle Scholar
  56. James DI, Parone PA, Mattenberger Y, Martinou JC (2003) hFis1, a novel component of the mammalian mitochondrial fission machinery. J Biol Chem 278: 36373–36379. Epub 2003 Jun 3. doi:10.1074/jbc.M303758200.PubMedGoogle Scholar
  57. Kabine M, El Kebbaj Z, Oaxaca-Castillo D, et al (2004) Peroxisome proliferator-activated receptors as regulators of lipid metabolism; tissue differential expression in adipose tissues during cold acclimatization and hibernation of jerboa (Jaculus orientalis). Biochimie 86: 763–770. doi:10.1016/j.biochi.2004.10.003.PubMedGoogle Scholar
  58. Karbowski M, Norris KL, Cleland MM, Jeong SY, Youle RJ (2006) Role of Bax and Bak in mitochondrial morphogenesis. Nature 443: 658–662. doi:10.1038/nature05111.PubMedGoogle Scholar
  59. Karbowski M, Neutzner A, Youle RJ (2007) The mitochondrial E3 ubiquitin ligase MARCH5 is required for Drp1 dependent mitochondrial division. J Cell Biol 178: 71–84. doi:10.1083/jcb.200611064.PubMedGoogle Scholar
  60. Kassmann CM, Lappe-Siefke C, Baes M, et al (2007) Axonal loss and neuroinflammation caused by peroxisome-deficient oligodendrocytes. Nat Genet 39: 969–976. doi:10.1038/ng2070.PubMedGoogle Scholar
  61. Kemper C, Habib SJ, Engl G, Heckmeyer P, Dimmer KS, Rapaport D (2008) Integration of tail-anchored proteins into the mitochondrial outer membrane does not require any known import components. J Cell Sci 121: 1990–1998. doi:10.1242/jcs.024034.PubMedGoogle Scholar
  62. Kiel JA, van der Klei IJ, van den Berg MA, Bovenberg RA, Veenhuis M (2005) Overproduction of a single protein, Pc-Pex11p, results in 2-fold enhanced penicillin production by Penicillium chrysogenum. Fungal Genet Biol 42: 154–164. Epub 2004 Dec 9. doi:10.1016/j.fgb.2004.10.010.PubMedGoogle Scholar
  63. Kim PK, Mullen RT, Schumann U, Lippincott-Schwartz J (2006) The origin and maintenance of mammalian peroxisomes involves a de novo PEX16-dependent pathway from the ER. J Cell Biol 173: 521–532. doi:10.1083/jcb.200601036.PubMedGoogle Scholar
  64. Kim I, Rodriguez-Enriquez S, Lemasters JJ (2007) Selective degradation of mitochondria by mitophagy. Arch Biochem Biophys 462: 245–253. doi:10.1016/ Scholar
  65. Kissova I, Deffieu M, Manon S, Camougrand N (2004) Uth1p is involved in the autophagic degradation of mitochondria. J Biol Chem 279: 39068–39074. doi:10.1074/jbc.M406960200.PubMedGoogle Scholar
  66. Kobayashi S, Tanaka A, Fujiki Y (2007) Fis1, DLP1, and Pex11p coordinately regulate peroxisome morphogenesis. Exp Cell Res 313: 1675–1686. doi:10.1016/j.yexcr.2007.02.028.PubMedGoogle Scholar
  67. Koch A, Thiemann M, Grabenbauer M, Yoon Y, McNiven MA, Schrader M (2003) Dynamin-like protein 1 is involved in peroxisomal fission. J Biol Chem 278: 8597–8605. doi:10.1074/jbc.M211761200.PubMedGoogle Scholar
  68. Koch A, Schneider G, Luers GH, Schrader M (2004) Peroxisome elongation and constriction but not fission can occur independently of dynamin-like protein 1. J Cell Sci 117: 3995–4006. doi:10.1242/jcs.01268.PubMedGoogle Scholar
  69. Koch A, Yoon Y, Bonekamp NA, McNiven MA, Schrader M (2005) A role for fis1 in both mitochondrial and peroxisomal fission in Mammalian cells. Mol Biol Cell 16: 5077–5086. Epub 2005 Aug 17. doi:10.1091/mbc.E05-02-0159.PubMedGoogle Scholar
  70. Koepke JI, Nakrieko KA, Wood CS, et al (2007) Restoration of peroxisomal catalase import in a model of human cellular aging. Traffic 8: 1590–1600. doi:10.1111/j.1600-0854.2007.00633.x.PubMedGoogle Scholar
  71. Koepke JI, Wood CS, Terlecky LJ, Walton PA, Terlecky SR (2008) Progeric effects of catalase inactivation in human cells. Toxicol Appl Pharmacol 232: 99–108.PubMedGoogle Scholar
  72. Kragt A, Voorn-Brouwer T, van den Berg M, Distel B (2005) Endoplasmic reticulum-directed Pex3p Routes to peroxisomes and restores peroxisome formation in a Saccharomyces cerevisiae pex3Delta strain. J Biol Chem 280: 34350–34357. Epub 2005 Aug 12. doi:10.1074/jbc.M505432200.PubMedGoogle Scholar
  73. Kunau WH (2005) Peroxisome biogenesis: end of the debate. Curr Biol 15: R774–R776. doi:10.1016/j.cub.2005.08.056.PubMedGoogle Scholar
  74. Kuravi K, Nagotu S, Krikken AM, et al (2006) Dynamin-related proteins Vps1p and Dnm1p control peroxisome abundance in Saccharomyces cerevisiae. J Cell Sci 119: 3994–4001. Epub 2006 Sep 12. doi:10.1242/jcs.03166.PubMedGoogle Scholar
  75. Lazarow PB (2003) Peroxisome biogenesis: advances and conundrums. Curr Opin Cell Biol 15: 489–497. doi:10.1016/S0955-0674(03)00082-6.PubMedGoogle Scholar
  76. Leon S, Goodman JM, Subramani S (2006) Uniqueness of the mechanism of protein import into the peroxisome matrix: transport of folded, co-factor-bound and oligomeric proteins by shuttling receptors. Biochim Biophys Acta 1763: 1552–1564. doi:10.1016/j.bbamcr.2006.08.037.PubMedGoogle Scholar
  77. Levak-Frank S, Radner H, Walsh A, et al (1995) Muscle-specific overexpression of lipoprotein lipase causes a severe myopathy characterized by proliferation of mitochondria and peroxisomes in transgenic mice. J Clin Invest 96: 976–986. doi:10.1172/JCI118145.PubMedGoogle Scholar
  78. Li X, Gould SJ (2003) The dynamin-like GTPase DLP1 is essential for peroxisome division and is recruited to peroxisomes in part by PEX11. J Biol Chem 278: 17012–17020. doi:10.1074/jbc.M212031200.PubMedGoogle Scholar
  79. Li Z, Okamoto K, Hayashi Y, Sheng M (2004) The importance of dendritic mitochondria in the morphogenesis and plasticity of spines and synapses. Cell 119: 873–887. doi:10.1016/j.cell.2004.11.003.PubMedGoogle Scholar
  80. Lill R, Muhlenhoff U (2005) Iron-sulfur-protein biogenesis in eukaryotes. Trends Biochem Sci 30: 133–141. doi:10.1016/j.tibs.2005.01.006.PubMedGoogle Scholar
  81. Lingard MJ, Gidda SK, Bingham S, Rothstein SJ, Mullen RT, Trelease RN (2008) Arabidopsis PEROXIN11c-e, FISSION1b, and DYNAMIN-RELATED PROTEIN3A cooperate in cell cycle-associated replication of peroxisomes. Plant Cell 20: 1567–1585.PubMedGoogle Scholar
  82. Mano S, Nakamori C, Kondo M, Hayashi M, Nishimura M (2004) An Arabidopsis dynamin-related protein, DRP3A, controls both peroxisomal and mitochondrial division. Plant J 38: 487–498. doi:10.1111/j.1365-313X.2004.02063.x.PubMedGoogle Scholar
  83. McBride HM, Neuspiel M, Wasiak S (2006) Mitochondria: more than just a powerhouse. Curr Biol 16: R551–R560. doi:10.1016/j.cub.2006.06.054.PubMedGoogle Scholar
  84. McGuinness MC, Lu JF, Zhang HP, et al (2003) Role of ALDP (ABCD1) and mitochondria in X-linked adrenoleukodystrophy. Mol Cell Biol 23: 744–753. doi:10.1128/MCB.23.2.744-753.2003.PubMedGoogle Scholar
  85. Meeusen S, McCaffery JM, Nunnari J (2004) Mitochondrial fusion intermediates revealed in vitro. Science 305: 1747–1752. doi:10.1126/science.1100612.PubMedGoogle Scholar
  86. Miller KE, Sheetz MP (2004) Axonal mitochondrial transport and potential are correlated. J Cell Sci 117: 2791–2804. doi:10.1242/jcs.01130.PubMedGoogle Scholar
  87. Moldovan L, Moldovan NI (2004) Oxygen free radicals and redox biology of organelles. Histochem Cell Biol 122: 395–412. Epub 2004 Sep 25. doi:10.1007/s00418-004-0676-y.PubMedGoogle Scholar
  88. Motley AM, Hettema EH (2007) Yeast peroxisomes multiply by growth and division. J Cell Biol 178: 399–410. doi:10.1083/jcb.200702167.PubMedGoogle Scholar
  89. Motley AM, Ward GP, Hettema EH (2008) Dnm1p-dependent peroxisome fission requires Caf4p, Mdv1p and Fis1p. J Cell Sci 121: 1633–1640. doi:10.1242/jcs.026344.PubMedGoogle Scholar
  90. Muench DG, Mullen RT (2003) Peroxisome dynamics in plant cells: a role for the cytoskeleton. Plant Science 164: 307–315. doi:10.1016/S0168-9452(02)00426-0.Google Scholar
  91. Mullen RT, Trelease RN (2000) The sorting signals for peroxisomal membrane-bound ascorbate peroxidase are within its C-terminal tail. J Biol Chem 275: 16337–16344. doi:10.1074/jbc.M001266200.PubMedGoogle Scholar
  92. Mullen RT, Trelease RN (2006) The ER-peroxisome connection in plants: development of the “ER semi-autonomous peroxisome maturation and replication” model for plant peroxisome biogenesis. Biochim Biophys Acta 1763: 1655–1668. doi:10.1016/j.bbamcr.2006.09.011.PubMedGoogle Scholar
  93. Mullen RT, Lisenbee CS, Miernyk JA, Trelease RN (1999) Peroxisomal membrane ascorbate peroxidase is sorted to a membranous network that resembles a subdomain of the endoplasmic reticulum. Plant Cell 11: 2167–2185.PubMedGoogle Scholar
  94. Nagotu S, Krikken AM, Otzen M, Kiel JA, Veenhuis M, van der Klei IJ (2008a) Peroxisome fission in Hansenula polymorpha requires Mdv1 and Fis1, two proteins also involved in mitochondrial fission. Traffic 9: 1471–1484.PubMedGoogle Scholar
  95. Nagotu S, Saraya R, Otzen M, Veenhuis M, van der Klei IJ (2008b) Peroxisome proliferation in Hansenula polymorpha requires Dnm1p which mediates fission but not de novo formation. Biochim Biophys Acta 1783: 760–769. doi:10.1016/j.bbamcr.2007.10.018.PubMedGoogle Scholar
  96. Nakada K, Inoue K, Ono T, et al (2001) Inter-mitochondrial complementation: mitochondria-specific system preventing mice from expression of disease phenotypes by mutant mtDNA. Nat Med 7: 934–940. doi:10.1038/90976.PubMedGoogle Scholar
  97. Nedergaard J, Alexson S, Cannon B (1980) Cold adaptation in the rat: increased brown fat peroxisomal beta-oxidation relative to maximal mitochondrial oxidative capacity. Am J Physiol 239: C208–C216.PubMedGoogle Scholar
  98. Neupert W, Herrmann JM (2007) Translocation of proteins into mitochondria. Annu Rev Biochem 76: 723–749. doi:10.1146/annurev.biochem.76.052705.163409.PubMedGoogle Scholar
  99. Neuspiel M, Schauss AC, Braschi E, et al (2008) Cargo-selected transport from the mitochondria to peroxisomes is mediated by vesicular carriers. Curr Biol 18: 102–108. doi:10.1016/j.cub.2007.12.038.PubMedGoogle Scholar
  100. Niemann A, Ruegg M, La Padula V, Schenone A, Suter U (2005) Ganglioside-induced differentiation associated protein 1 is a regulator of the mitochondrial network: new implications for Charcot–Marie–Tooth disease. J Cell Biol 170: 1067–1078. Epub 2005 Sep 19. doi:10.1083/jcb.200507087.PubMedGoogle Scholar
  101. Nito K, Yamaguchi K, Kondo M, Hayashi M, Nishimura M (2001) Pumpkin peroxisomal ascorbate peroxidase is localized on peroxisomal membranes and unknown membranous structures. Plant Cell Physiol 42: 20–27. doi:10.1093/pcp/pce003.PubMedGoogle Scholar
  102. Novikoff AB, Shin WY (1964) The endoplasmic reticulum in the Golgi zone and its relations to microbodies, Golgi apparatus, and autophagic vacuoles in rat liver cells. J Microsc 3: 187–206.Google Scholar
  103. Okamoto K, Shaw JM (2005) Mitochondrial morphology and dynamics in yeast and multicellular eukaryotes. Annu Rev Genet 39: 503–536. doi:10.1146/annurev.genet.38.072902.093019.PubMedGoogle Scholar
  104. Okamoto K, Nagai T, Miyawaki A, Hayashi Y (2004) Rapid and persistent modulation of actin dynamics regulates postsynaptic reorganization underlying bidirectional plasticity. Nat Neurosci 7: 1104–1112. doi:10.1038/nn1311.PubMedGoogle Scholar
  105. Platta HW, Erdmann R (2007) Peroxisomal dynamics. Trends Cell Biol 17: 474–484. doi:10.1016/j.tcb.2007.06.009.PubMedGoogle Scholar
  106. Poirier Y, Antonenkov VD, Glumoff T, Hiltunen JK (2006) Peroxisomal beta-oxidation—a metabolic pathway with multiple functions. Biochim Biophys Acta 1763: 1413–1426. doi:10.1016/j.bbamcr.2006.08.034.PubMedGoogle Scholar
  107. Pollera M, Locci-Cubeddu T, Bergamini E (1983) Effect of cold adaptation on liver peroxisomes and peroxisomal oxidative activities of rat. A morphometric/stereologic and biochemical study. Arch Int Physiol Biochim 91: 35–42. doi:10.3109/13813458309106476.PubMedGoogle Scholar
  108. Praefcke GJ, McMahon HT (2004) The dynamin superfamily: universal membrane tubulation and fission molecules? Nat Rev Mol Cell Biol 5: 133–147. doi:10.1038/nrm1313.PubMedGoogle Scholar
  109. Priault M, Salin B, Schaeffer J, Vallette FM, di Rago JP, Martinou JC (2005) Impairing the bioenergetic status and the biogenesis of mitochondria triggers mitophagy in yeast. Cell Death Differ 12: 1613–1621. doi:10.1038/sj.cdd.4401697.PubMedGoogle Scholar
  110. Raychaudhuri S, Prinz WA (2008) Nonvesicular phospholipid transfer between peroxisomes and the endoplasmic reticulum. Proc Natl Acad Sci U S A 105: 15785–15790. doi:10.1073/pnas.0808321105.PubMedGoogle Scholar
  111. Rizzuto R, Bernardi P, Pozzan T (2000) Mitochondria as all-round players of the calcium game. J Physiol 529(Pt 1): 37–47. doi:10.1111/j.1469-7793.2000.00037.x.PubMedGoogle Scholar
  112. Sacksteder KA, Jones JM, South ST, Li X, Liu Y, Gould SJ (2000) PEX19 binds multiple peroxisomal membrane proteins, is predominantly cytoplasmic, and is required for peroxisome membrane synthesis. J Cell Biol 148: 931–944. doi:10.1083/jcb.148.5.931.PubMedGoogle Scholar
  113. Sakai Y, Oku M, van der Klei IJ, Kiel JA (2006) Pexophagy: autophagic degradation of peroxisomes. Biochim Biophys Acta 1763: 1767–1775. doi:10.1016/j.bbamcr.2006.08.023.PubMedGoogle Scholar
  114. Santel A, Frank S (2008) Shaping mitochondria: the complex posttranslational regulation of the mitochondrial fission protein DRP1. IUBMB Life 60: 448–455. doi:10.1002/iub.71.PubMedGoogle Scholar
  115. Santos MJ, Quintanilla RA, Toro A, et al (2005) Peroxisomal proliferation protects from beta-amyloid neurodegeneration. J Biol Chem 280: 41057–41068. doi:10.1074/jbc.M505160200.PubMedGoogle Scholar
  116. Scheckhuber CQ, Erjavec N, Tinazli A, Hamann A, Nystrom T, Osiewacz HD (2007) Reducing mitochondrial fission results in increased life span and fitness of two fungal ageing models. Nat Cell Biol 9: 99–105. doi:10.1038/ncb1524.PubMedGoogle Scholar
  117. Schrader M (2006) Shared components of mitochondrial and peroxisomal division. Biochim Biophys Acta 1763: 531–541. doi:10.1016/j.bbamcr.2006.01.004.PubMedGoogle Scholar
  118. Schrader M, Fahimi HD (2006a) Peroxisomes and oxidative stress. Biochim Biophys Acta 1763: 1755–1766. doi:10.1016/j.bbamcr.2006.09.006.PubMedGoogle Scholar
  119. Schrader M, Fahimi HD (2006b) Growth and division of peroxisomes. Int Rev Cytol 255: 237–290. doi:10.1016/S0074-7696(06)55005-3.PubMedGoogle Scholar
  120. Schrader M, Fahimi HD (2008) The peroxisome: still a mysterious organelle. Histochem Cell Biol 129: 421–440. doi:10.1007/s00418-008-0396-9.PubMedGoogle Scholar
  121. Schrader M, Yoon Y (2007) Mitochondria and peroxisomes: are the ‘Big Brother’ and the ‘Little Sister’ closer than assumed? Bioessays 29: 1105–1114. doi:10.1002/bies.20659.PubMedGoogle Scholar
  122. Schrader M, Burkhardt JK, Baumgart E, et al (1996) Interaction of microtubules with peroxisomes. Tubular and spherical peroxisomes in HepG2 cells and their alterations induced by microtubule-active drugs. Eur J Cell Biol 69: 24–35.PubMedGoogle Scholar
  123. Schrader M, Reuber BE, Morrell JC, et al (1998) Expression of PEX11beta mediates peroxisome proliferation in the absence of extracellular stimuli. J Biol Chem 273: 29607–29614. doi:10.1074/jbc.273.45.29607.PubMedGoogle Scholar
  124. Schrader M, King SJ, Stroh TA, Schroer TA (2000) Real time imaging reveals a peroxisomal reticulum in living cells. J Cell Sci 113: 3663–3671.PubMedGoogle Scholar
  125. Schrader M, Thiemann M, Fahimi HD (2003) Peroxisomal motility and interaction with microtubules. Microsc Res Tech 61: 171–178. doi:10.1002/jemt.10326.PubMedGoogle Scholar
  126. Schriner SE, Linford NJ, Martin GM, et al (2005) Extension of murine life span by overexpression of catalase targeted to mitochondria. Science 308: 1909–1911. doi:10.1126/science.1106653.PubMedGoogle Scholar
  127. Schumann U, Subramani S (2008) Special delivery from mitochondria to peroxisomes. Trends Cell Biol 18: 253–256. doi:10.1016/j.tcb.2008.04.002.PubMedGoogle Scholar
  128. Setoguchi K, Otera H, Mihara K (2006) Cytosolic factor- and TOM-independent import of C-tail-anchored mitochondrial outer membrane proteins. EMBO J 25: 5635–5647. doi:10.1038/sj.emboj.7601438.PubMedGoogle Scholar
  129. Skulachev VP (2001) Mitochondrial filaments and clusters as intracellular power-transmitting cables. Trends Biochem Sci 26: 23–29. doi:10.1016/S0968-0004(00)01735-7.PubMedGoogle Scholar
  130. 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.PubMedGoogle Scholar
  131. Song BD, Schmid SL (2003) A molecular motor or a regulator? Dynamin’s in a class of its own. Biochemistry 42: 1369–1376. doi:10.1021/bi027062h.PubMedGoogle Scholar
  132. Soukupova M, Sprenger C, Gorgas K, Kunau WH, Dodt G (1999) Identification and characterization of the human peroxin PEX3. Eur J Cell Biol 78: 357–374.PubMedGoogle Scholar
  133. Steinberg SJ, Dodt G, Raymond GV, Braverman NE, Moser AB, Moser HW (2006) Peroxisome biogenesis disorders. Biochim Biophys Acta 1763: 1733–1748. doi:10.1016/j.bbamcr.2006.09.010.PubMedGoogle Scholar
  134. Stojanovski D, Koutsopoulos OS, Okamoto K, Ryan MT (2004) Levels of human Fis1 at the mitochondrial outer membrane regulate mitochondrial morphology. J Cell Sci 117: 1201–1210. doi:10.1242/jcs.01058.PubMedGoogle Scholar
  135. Stowers RS, Megeath LJ, Gorska-Andrzejak J, Meinertzhagen IA, Schwarz TL (2002) Axonal transport of mitochondria tosynapses depends on milton, a novel Drosophila protein.Neuron 36: 1063–1077. doi:10.1016/S0896-6273(02)01094-2.PubMedGoogle Scholar
  136. Subramani S (1998) Components involved in peroxisome import, biogenesis, proliferation, turnover, and movement. Physiol Rev 78: 171–188.PubMedGoogle Scholar
  137. Suen DF, Norris KL, Youle RJ (2008) Mitochondrial dynamics and apoptosis. Genes Dev 22: 1577–1590. doi:10.1101/gad.1658508.PubMedGoogle Scholar
  138. Szabadkai G, Simoni AM, Chami M, Wieckowski MR, Youle RJ, Rizzuto R (2004) Drp-1-dependent division of the mitochondrial network blocks intraorganellar Ca2+ waves and protects against Ca2+-mediated apoptosis. Mol Cell 16: 59–68. doi:10.1016/j.molcel.2004.09.026.PubMedGoogle Scholar
  139. Tabak HF, Hoepfner D, Zand A, Geuze HJ, Braakman I, Huynen MA (2006) Formation of peroxisomes: present and past. Biochim Biophys Acta 1763: 1647–1654. doi:10.1016/j.bbamcr.2006.08.045.PubMedGoogle Scholar
  140. Taguchi N, Ishihara N, Jofuku A, Oka T, Mihara K (2007) Mitotic phosphorylation of dynamin-related GTPase Drp1 participates in mitochondrial fission. J Biol Chem 282: 11521–11529. doi:10.1074/jbc.M607279200.PubMedGoogle Scholar
  141. Tam YY, Fagarasanu A, Fagarasanu M, Rachubinski RA (2005) Pex3p initiates the formation of a preperoxisomal compartment from a subdomain of the endoplasmic reticulum in Saccharomyces cerevisiae. J Biol Chem 280: 34933–34939. Epub 2005 Aug 8. doi:10.1074/jbc.M506208200.PubMedGoogle Scholar
  142. Tanaka A, Kobayashi S, Fujiki Y (2006) Peroxisome division is impaired in a CHO cell mutant with an inactivating point-mutation in dynamin-like protein 1 gene. Exp Cell Res 312: 1671–1684. doi:10.1016/j.yexcr.2006.01.028.PubMedGoogle Scholar
  143. Terlecky SR, Koepke JI, Walton PA (2006) Peroxisomes and aging. Biochim Biophys Acta 1763: 1749–1754. doi:10.1016/j.bbamcr.2006.08.017.PubMedGoogle Scholar
  144. Thoms S, Erdmann R (2005) Dynamin-related proteins and Pex11 proteins in peroxisome division and proliferation. FEBS J 272: 5169–5181. doi:10.1111/j.1742-4658.2005.04939.x.PubMedGoogle Scholar
  145. Twig G, Elorza A, Molina AJ, et al (2008a) Fission and selective fusion govern mitochondrial segregation and elimination by autophagy. EMBO J 27: 433–446. doi:10.1038/sj.emboj.7601963.PubMedGoogle Scholar
  146. Twig G, Hyde B, Shirihai OS (2008b) Mitochondrial fusion, fission and autophagy as a quality control axis: the bioenergetic view. Biochim Biophys Acta 1777: 1092–1097.Google Scholar
  147. Van Ael E, Fransen M (2006) Targeting signals in peroxisomal membrane proteins. Biochim Biophys Acta 1763: 1629–1638. doi:10.1016/j.bbamcr.2006.08.020.PubMedGoogle Scholar
  148. Verstreken P, Ly CV, Venken KJ, Koh TW, Zhou Y, Bellen HJ (2005) Synaptic mitochondria are critical for mobilization of reserve pool vesicles at Drosophila neuromuscular junctions. Neuron 47: 365–378. doi:10.1016/j.neuron.2005.06.018.PubMedGoogle Scholar
  149. Visser WF, van Roermund CW, Ijlst L, Waterham HR, Wanders RJ (2007) Metabolite transport across the peroxisomal membrane. Biochem J 401: 365–375. doi:10.1042/BJ20061352.PubMedGoogle Scholar
  150. Wallace DC (2005) A mitochondrial paradigm of metabolic and degenerative diseases, aging, and cancer: a dawn for evolutionary medicine. Annu Rev Genet 39: 359–407. doi:10.1146/annurev.genet.39.110304.095751.PubMedGoogle Scholar
  151. Walther DM, Rapaport D (2008) Biogenesis of mitochondrial outer membrane proteins. Biochim Biophys Acta 1793: 42–51.PubMedGoogle Scholar
  152. Wanders RJ (2004) Peroxisomes, lipid metabolism, and peroxisomal disorders. Mol Genet Metab 83: 16–27. doi:10.1016/j.ymgme.2004.08.016.PubMedGoogle Scholar
  153. Wanders RJ, Waterham HR (2005) Peroxisomal disorders I: biochemistry and genetics of peroxisome biogenesis disorders. Clin Genet 67: 107–133. doi:10.1111/j.1399-0004.2004.00329.x.PubMedGoogle Scholar
  154. Wanders RJ, Waterham HR (2006a) Peroxisomal disorders: the single peroxisomal enzyme deficiencies. Biochim Biophys Acta 1763: 1707–1720. doi:10.1016/j.bbamcr.2006.08.010.PubMedGoogle Scholar
  155. Wanders RJA, Waterham HR (2006b) Biochemistry of mammalian peroxisomes revisited. Annu Rev Biochem 75: 295–332. doi:10.1146/annurev.biochem.74.082803.133329.PubMedGoogle Scholar
  156. Wasiak S, Zunino R, McBride HM (2007) Bax/Bak promote sumoylation of DRP1 and its stable association with mitochondria during apoptotic cell death. J Cell Biol 177: 439–450. doi:10.1083/jcb.200610042.PubMedGoogle Scholar
  157. Waterham HR, Koster J, van Roermund CW, Mooyer PA, Wanders RJ, Leonard JV (2007) A lethal defect of mitochondrial and peroxisomal fission. N Engl J Med 356: 1736–1741. doi:10.1056/NEJMoa064436.PubMedGoogle Scholar
  158. Wattenberg B, Lithgow T (2001) Targeting of C-terminal (tail)-anchored proteins: understanding how cytoplasmic activities are anchored to intracellular membranes. Traffic 2: 66–71. doi:10.1034/j.1600-0854.2001.20108.x.PubMedGoogle Scholar
  159. Wiese S, Gronemeyer T, Ofman R, et al (2007) Proteomic characterization of mouse kidney peroxisomes by tandem mass spectrometry and protein correlation profiling. Mol Cell Proteomics 6: 2045–2057.PubMedGoogle Scholar
  160. Yamamoto K, Fahimi HD (1987) Three-dimensional reconstruction of a peroxisomal reticulum in regenerating rat liver: evidence of interconnections between heterogeneous segments. J Cell Biol 105: 713–722. doi:10.1083/jcb.105.2.713.PubMedGoogle Scholar
  161. Yan M, Rayapuram N, Subramani S (2005) The control of peroxisome number and size during division and proliferation. Curr Opin Cell Biol 17: 376–383. doi:10.1016/ Scholar
  162. Yoon Y, Krueger EW, Oswald BJ, McNiven MA (2003) The mitochondrial protein hFis1 regulates mitochondrial fission in mammalian cells through an interaction with the dynamin-like protein DLP1. Mol Cell Biol 23: 5409–5420. doi:10.1128/MCB.23.15.5409-5420.2003.PubMedGoogle Scholar
  163. Youle RJ, Karbowski M (2005) Mitochondrial fission in apoptosis. Nat Rev Mol Cell Biol 6: 657–663. doi:10.1038/nrm1697.PubMedGoogle Scholar
  164. Yu T, Fox RJ, Burwell LS, Yoon Y (2005) Regulation of mitochondrial fission and apoptosis by the mitochondrial outer membrane protein hFis1. J Cell Sci 118: 4141–4151. Epub 2005 Aug 23. doi:10.1242/jcs.02537.PubMedGoogle Scholar
  165. Yu T, Robotham JL, Yoon Y (2006) Increased production of reactive oxygen species in hyperglycemic conditions requires dynamic change of mitochondrial morphology. Proc Natl Acad Sci U S A 103: 2653–2658. doi:10.1073/pnas.0511154103.PubMedGoogle Scholar
  166. Zuchner S, Vance JM (2005) Emerging pathways for hereditary axonopathies. J Mol Med 83: 935–943. doi:10.1007/s00109-005-0694-9.PubMedGoogle Scholar
  167. Zunino R, Schauss A, Rippstein P, Andrade-Navarro M, McBride HM (2007) The SUMO protease SENP5 is required to maintain mitochondrial morphology and function. J Cell Sci 120: 1178–1188. doi:10.1242/jcs.03418.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2008

Authors and Affiliations

  • F. Camões
    • 1
  • N. A. Bonekamp
    • 1
  • H. K. Delille
    • 1
  • M. Schrader
    • 1
  1. 1.Centre for Cell Biology & Department of BiologyUniversity of AveiroAveiroPortugal

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