Advertisement

The Interplay between BCL-2 Family Proteins and Mitochondrial Morphology in the Regulation of Apoptosis

  • Maria Eugenia Soriano
  • Luca Scorrano
Part of the Advances in Experimental Medicine and Biology book series (volume 687)

Abstract

Apoptosis is a highly regulated process where key players such as BCL-2 family members control the recruitment of the mitochondrial subroutine. This culminates in the release of cytochrome c from the organelle in the cytoplasm, where it is required for the activation of effector caspases. The complete release of cytochrome c is the result of the combined action of proapoptotic BCL-2 family members and of changes in the complex morphology and ultrastructure of the organelle, controlled by the balance between fusion and fission processes. Here we discuss recent findings pointing to a role for changes in mitochondrial morphology during apoptosis and how these might be regulated by members of the BCL-2 family.

Keywords

Antiapoptotic Protein Mitochondrial Fission Mitochondrial Morphology Mitochondrial Fusion Cell Death Differ 
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.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Vaux DL, Cory S, Adams JM. BCL-2 gene promotes haemopoietic cell survival and cooperates with c-myc to immortalize preB-cells. Nature 1988; 335:440–442.PubMedGoogle Scholar
  2. 2.
    Nunez G, Seto M, Seremetis S et al. Growth-and tumor-promoting effects of deregulated BCL2 in human B-lymphoblastoid cells. Proc Natl Acad Sci USA 1989; 86:4589–4593.PubMedGoogle Scholar
  3. 3.
    Hockenbery D, Nunez G, Milliman C et al. BCL-2 is an inner mitochondrial membrane protein that blocks programmed cell death. Nature 1990; 348:334–336.PubMedGoogle Scholar
  4. 4.
    McDonnell TJ, Nunez G, Platt FM et al. Deregulated BCL-2-immunoglobulin transgene expands a resting but responsive immunoglobulin M and D-expressing B-cell population. Mol Cell Biol 1990; 10:1901–1907.PubMedGoogle Scholar
  5. 5.
    Nunez G, London L, Hockenbery D et al. Deregulated BCL-2 gene expression selectively prolongs survival of growth factor-deprived hemopoietic cell lines. J Immunol 1990; 144:3602–3610.PubMedGoogle Scholar
  6. 6.
    Scaffidi C, Fulda S, Srinivasan A et al. Two CD95 (APO-1/Fas) signaling pathways. EMBO J 1998; 17:1675–1687.PubMedGoogle Scholar
  7. 7.
    Scaffidi C, Schmitz I, Zha J et al. Differential modulation of apoptosis sensitivity in CD95 type I and type II cells. J Biol Chem 1999; 274:22532–22538.PubMedGoogle Scholar
  8. 8.
    Medema JP, Scaffidi C, Kischkel FC et al. FLICE is activated by association with the CD95 death-inducing signaling complex (DISC). EMBO J 1997; 16:2794–2804.PubMedGoogle Scholar
  9. 9.
    Peter ME, Kischkel FC, Hellbardt S et al. CD95 (APO-1/Fas)-associating signalling proteins. Cell Death Differ 1996; 3:161–170.PubMedGoogle Scholar
  10. 10.
    Chinnaiyan AM, Tepper CG, Seldin MF et al. FADD/MORT1 is a common mediator of CD95 (Fas/ APO-1) and tumor necrosis factor receptor-induced apoptosis. J Biol Chem 1996; 271:4961–4965.PubMedGoogle Scholar
  11. 11.
    Gross A, Yin XM, Wang K et al. Caspase cleaved BID targets mitochondria and is required for cytochrome c release, while BCL-XL prevents this release but not tumor necrosis factor-R1/Fas death. J Biol Chem 1999; 274:1156–1163.PubMedGoogle Scholar
  12. 12.
    Luo X, Budihardjo I, Zou H et al. Bid, a Bcl2 interacting protein, mediates cytochrome c release from mitochondria in response to activation of cell surface death receptors. Cell 1998; 94:481–490.PubMedGoogle Scholar
  13. 13.
    Yin XM, Wang K, Gross A et al. Bid-deficient mice are resistant to Fas-induced hepatocellular apoptosis. Nature 1999; 400:886–891.PubMedGoogle Scholar
  14. 14.
    Rich T, Allen RL, Wyllie AH. Defying death after DNA damage. Nature 2000; 407:777–783.PubMedGoogle Scholar
  15. 15.
    Blank M, Shiloh Y. Programs for cell death: apoptosis is only one way to go. Cell Cycle 2007; 6:686–695.PubMedGoogle Scholar
  16. 16.
    Roos WP, Kaina B. DNA damage-induced cell death by apoptosis. Trends Mol Med 2006; 12:440–450.PubMedGoogle Scholar
  17. 17.
    Gottlieb E, Armour SM, Thompson CB. Mitochondrial respiratory control is lost during growth factor deprivation. Proc Natl Acad Sci USA 2002; 99:12801–12806.PubMedGoogle Scholar
  18. 18.
    Saikumar P, Dong Z, Patel Y et al. Role of hypoxia-induced Bax translocation and cytochrome c release in reoxygenation injury. Oncogene 1998; 17:3401–3415.PubMedGoogle Scholar
  19. 19.
    Danial NN, Korsmeyer SJ. Cell death: critical control points. Cell 2004; 116:205–219.PubMedGoogle Scholar
  20. 20.
    Oltvai ZN, Milliman CL, Korsmeyer SJ. BCL-2 heterodimerizes in vivo with a conserved homolog, Bax, that accelerates programmed cell death. Cell 1993; 74:609–619.PubMedGoogle Scholar
  21. 21.
    Korsmeyer SJ, Shutter JR, Veis DJ et al. BCL-2/Bax: a rheostat that regulates an anti-oxidant pathway and cell death. Semin Cancer Biol 1993; 4:327–332.PubMedGoogle Scholar
  22. 22.
    Matsuyama S, Schendel SL, Xie Z et al. Cytoprotection by BCL-2 requires the pore-forming alpha5 and alpha6 helices. J Biol Chem 1998; 273:30995–31001.PubMedGoogle Scholar
  23. 23.
    Minn AJ, Velez P, Schendel SL et al. Bcl-x(L) forms an ion channel in synthetic lipid membranes. Nature 1997; 385:353–357.PubMedGoogle Scholar
  24. 24.
    Schendel SL, Xie Z, Montal MO et al. Channel formation by antiapoptotic protein BCL-2. Proc Natl Acad Sci USA 1997; 94:5113–5118.PubMedGoogle Scholar
  25. 25.
    Heimlich G, McKinnon AD, Bernardo K et al. Bax-induced cytochrome c release from mitochondria depends on alpha-helices-5 and-6. Biochem J 2004; 378:247–255.PubMedGoogle Scholar
  26. 26.
    Muchmore SW, Sattler M, Liang H et al. X-ray and NMR structure of human Bcl-xL, an inhibitor of programmed cell death. Nature 1996; 381:335–341.PubMedGoogle Scholar
  27. 27.
    Huang DC, Strasser A. BH3-Only proteins-essential initiators of apoptotic cell death. Cell 2000; 103:839–842.PubMedGoogle Scholar
  28. 28.
    Lutz RJ. Role of the BH3 (BCL-2 homology 3) domain in the regulation of apoptosis and BCL-2-related proteins. Biochem Soc Trans 2000; 28:51–56.PubMedGoogle Scholar
  29. 29.
    Nouraini S, Six E, Matsuyama S et al. The putative pore-forming domain of Bax regulates mitochondrial localization and interaction with Bcl-X(L). Mol Cell Biol 2000; 20:1604–1615.PubMedGoogle Scholar
  30. 30.
    Borner C. The BCL-2 protein family: sensors and checkpoints for life-or-death decisions. Mol Immunol 2003; 39:615–647.PubMedGoogle Scholar
  31. 31.
    Petros AM, Dinges J, Augeri DJ et al. Discovery of a potent inhibitor of the antiapoptotic protein Bcl-xL from NMR and parallel synthesis. J Med Chem 2006; 49:656–663.PubMedGoogle Scholar
  32. 32.
    Petros AM, Olejniczak ET, Fesik SW. Structural biology of the BCL-2 family of proteins. Biochim Biophys Acta 2004; 1644:83–94.PubMedGoogle Scholar
  33. 33.
    Petros AM, Medek A, Nettesheim DG et al. Solution structure of the antiapoptotic protein bcl-2. Proc Natl Acad Sci USA 2001; 98:3012–3017.PubMedGoogle Scholar
  34. 34.
    Petros AM, Nettesheim DG, Wang Y et al. Rationale for Bcl-xL/Bad peptide complex formation from structure, mutagenesis and biophysical studies. Protein Sci 2000; 9:2528–2534.PubMedGoogle Scholar
  35. 35.
    Gratiot-Deans J, Merino R, Nunez G et al. BCL-2 expression during T-cell development: early loss and late return occur at specific stages of commitment to differentiation and survival. Proc Natl Acad Sci USA 1994; 91:10685–10689.PubMedGoogle Scholar
  36. 36.
    Gratiot-Deans J, Ding L, Turka LA et al. BCL-2 proto-oncogene expression during human T-cell development. Evidence for biphasic regulation. J Immunol 1993; 151:83–91.PubMedGoogle Scholar
  37. 37.
    Chao DT, Korsmeyer SJ. BCL-XL-regulated apoptosis in T-cell development. Int Immunol 1997; 9:1375–1384.PubMedGoogle Scholar
  38. 38.
    Chao DT, Linette GP, Boise LH et al. BCL-XL and BCL-2 repress a common pathway of cell death. J Exp Med 1995; 182:821–828.PubMedGoogle Scholar
  39. 39.
    Moller C, Karlberg M, Abrink M et al. BCL-2 and BCL-XL are indispensable for the late phase of mast cell development from mouse embryonic stem cells. Exp Hematol 2007; 35:385–393.PubMedGoogle Scholar
  40. 40.
    Kamada S, Shimono A, Shinto Y et al. BCL-2 deficiency in mice leads to pleiotropic abnormalities: accelerated lymphoid cell death in thymus and spleen, polycystic kidney, hair hypopigmentation and distorted small intestine. Cancer Res 1995; 55:354–359.PubMedGoogle Scholar
  41. 41.
    Veis DJ, Sorenson CM, Shutter JR et al. BCL-2-deficient mice demonstrate fulminant lymphoid apoptosis, polycystic kidneys and hypopigmented hair. Cell 1993; 55:229–240.Google Scholar
  42. 42.
    Nakayama K, Nakayama K, Negishi I et al. Targeted disruption of BCL-2 alpha beta in mice: occurrence of gray hair, polycystic kidney disease and lymphocytopenia. Proc Natl Acad Sci USA 1994; 91:3700–3704.PubMedGoogle Scholar
  43. 43.
    Deaciuc I, D’Souza N, Nikolova-Karakashian M et al. The regulation of Fas (CD95/Apo-1)-mediated liver apoptosis in Kupffer cell-depleted mice. Hepatol Res 2002; 24:192.PubMedGoogle Scholar
  44. 44.
    Gibson L, Holmgreen SP, Huang DC et al. BCL-2, a novel member of the bcl-2 family, promotes cell survival. Oncogene 1996; 13:665–675.PubMedGoogle Scholar
  45. 45.
    Hamner S, Skoglosa Y, Lindholm D. Differential expression of bcl-w and bcl-x messenger RNA in the developing and adult rat nervous system. Neuroscience 1999; 91:673–684.PubMedGoogle Scholar
  46. 46.
    Dominov JA, Houlihan-Kawamoto CA, Swap CJ et al. Pro-and anti-apoptotic members of the BCL-2 family in skeletal muscle: a distinct role for BCL-2 in later stages of myogenesis. Dev Dyn 2001; 220:18–26.PubMedGoogle Scholar
  47. 47.
    O’Reilly LA, Print C, Hausmann G et al. Tissue expression and subcellular localization of the pro-survival molecule BCL-2. Cell Death Differ 2001; 8:486–494.PubMedGoogle Scholar
  48. 48.
    Yan W, Suominen J, Samson M et al. Involvement of BCL-2 family proteins in germ cell apoptosis during testicular development in the rat and pro-survival effect of stem cell factor on germ cells in vitro. Mol Cell Endocrinol 2000; 165:115–129.PubMedGoogle Scholar
  49. 49.
    Yan W, Samson M, Jegou B et al. BCL-2 forms complexes with Bax and Bak and elevated ratios of Bax/BCL-2 and Bak/BCL-2 correspond to spermatogonial and spermatocyte apoptosis in the testis. Mol Endocrinol 2000; 14:682–699.PubMedGoogle Scholar
  50. 50.
    Print CG, Loveland KL, Gibson L et al. Apoptosis regulator bcl-w is essential for spermatogenesis but appears otherwise redundant. Proc Natl Acad Sci USA 1998; 95:12424–12431.PubMedGoogle Scholar
  51. 51.
    Hershko A, Ciechanover A. The ubiquitin system. Annu Rev Biochem 1998; 67:425–479.PubMedGoogle Scholar
  52. 52.
    Cuconati A, Mukherjee C, Perez D et al. DNA damage response and MCL-1 destruction initiate apoptosis in adenovirus-infected cells. Genes Dev 2003; 17:2922–2932.PubMedGoogle Scholar
  53. 53.
    Opferman JT, Letai A, Beard C et al. Development and maintenance of B-and T-lymphocytes requires antiapoptotic MCL-1. Nature 2003; 426:671–676.PubMedGoogle Scholar
  54. 54.
    Chen L, Willis SN, Wei A et al. Differential targeting of prosurvival BCL-2 proteins by their BH3-only ligands allows complementary apoptotic function. Mol Cell 2005; 17:393–403.PubMedGoogle Scholar
  55. 55.
    Wang K, Gross A, Waksman G et al. Mutagenesis of the BH3 domain of BAX identifies residues critical for dimerization and killing. Mol Cell Biol 1998; 18:6083–6089.PubMedGoogle Scholar
  56. 56.
    Dzhagalov I, Dunkle A, He YW. The anti-apoptotic BCL-2 family member Mcl-1 promotes T-lymphocyte survival at multiple stages. J Immunol 2008; 181:521–528.PubMedGoogle Scholar
  57. 57.
    Rinkenberger JL, Horning S, Klocke B et al. Mcl-1 deficiency results in peri-implantation embryonic lethality. Genes Dev 2000; 14(1):23–714:23–27.PubMedGoogle Scholar
  58. 58.
    Opferman JT, Iwasaki H, Ong CC et al. Obligate role of anti-apoptotic MCL-1 in the survival of hematopoietic stem cells. Science 2005; 307:1101–1104.PubMedGoogle Scholar
  59. 59.
    Kaufmann SH, Karp JE, Svingen PA et al. Elevated expression of the apoptotic regulator Mcl-1 at the time of leukemic relapse. Blood 1998; 91:991–1000.PubMedGoogle Scholar
  60. 60.
    Zhou P, Levy NB, Xie H et al. MCL1 transgenic mice exhibit a high incidence of B-cell lymphoma manifested as a spectrum of histologic subtypes. Blood 2001; 97:3902–3909.PubMedGoogle Scholar
  61. 61.
    Ko JK, Lee MJ, Cho SH et al. Bfl-1S, a novel alternative splice variant of Bfl-1, localizes in the nucleus via its C-terminus and prevents cell death. Oncogene 2003; 22:2457–2465.PubMedGoogle Scholar
  62. 62.
    Somogyi RD, Wu Y, Orlofsky A et al. Transient expression of the BCL-2 family member, A1-a, results in nuclear localization and resistance to staurosporine-induced apoptosis. Cell Death Differ 2001; 8:785–793.PubMedGoogle Scholar
  63. 63.
    Grumont RJ, Rourke IJ, Gerondakis S. Rel-dependent induction of A1 transcription is required to protect B-cells from antigen receptor ligation-induced apoptosis. Genes Dev 1999; 13:400–411.PubMedGoogle Scholar
  64. 64.
    Kucharczak JF, Simmons MJ, Duckett CS et al. Constitutive proteasome-mediated turnover of Bfl-1/ A1 and its processing in response to TNF receptor activation in FL5.12 pro-B-cells convert it into a prodeath factor. Cell Death Differ 2005; 12:1225–1239.PubMedGoogle Scholar
  65. 65.
    Zhang H, Cowan-Jacob SW, Simonen M et al. Structural basis of BFL-1 for its interaction with BAX and its anti-apoptotic action in mammalian and yeast cells. J Biol Chem 2000; 275:11092–11099.PubMedGoogle Scholar
  66. 66.
    Sedlak TW, Oltvai ZN, Yang E et al. Multiple BCL-2 family members demonstrate selective dimerizations with Bax. Proc Natl Acad Sci USA 1995; 92:7834–7838.PubMedGoogle Scholar
  67. 67.
    Hirotani M, Zhang Y, Fujita N et al. NH2-terminal BH4 domain of BCL-2 is functional for heterodimerization with Bax and inhibition of apoptosis. J Biol Chem 1999; 274:20415–20420.PubMedGoogle Scholar
  68. 68.
    Werner AB, de VE, Tait SW et al. BCL-2 family member Bfl-1/A1 sequesters truncated bid to inhibit is collaboration with pro-apoptotic Bak or Bax. J Biol Chem 2002; 277:22781–22788.PubMedGoogle Scholar
  69. 69.
    Suzuki M, Youle RJ, Tjandra N. Structure of Bax: coregulation of dimer formation and intracellular localization. Cell 2000; 103:645–654.PubMedGoogle Scholar
  70. 70.
    Nechushtan A, Smith CL, Hsu YT et al. Conformation of the Bax C-terminus regulates subcellular location and cell death. EMBO J 1999; 18:2330–2341.PubMedGoogle Scholar
  71. 71.
    Jurgensmeier JM, Xie Z, Deveraux Q et al. Bax directly induces release of cytochrome c from isolated mitochondria. Proc Natl Acad Sci USA 1998; 95:4997–5002.PubMedGoogle Scholar
  72. 72.
    Hsu YT, Wolter KG, Youle RJ. Cytosol-to-membrane redistribution of Bax and Bcl-X(L) during apoptosis. Proc Natl Acad Sci USA 1997; 94:3668–3672.PubMedGoogle Scholar
  73. 73.
    Annis MG, Soucie EL, Dlugosz PJ et al. Bax forms multispanning monomers that oligomerize to permeabilize membranes during apoptosis. EMBO J 2005; 24:2096–2103.PubMedGoogle Scholar
  74. 74.
    Antignani A, Youle RJ. How do Bax and Bak lead to permeabilization of the outer mitochondrial membrane? Curr Opin Cell Biol 2006; 18:685–689.PubMedGoogle Scholar
  75. 75.
    Chipuk JE, Green DR. How do BCL-2 proteins induce mitochondrial outer membrane permeabilization? Trends Cell Biol 2008; 18:157–164.PubMedGoogle Scholar
  76. 76.
    Schlesinger PH, Gross A, Yin XM et al. Comparison of the ion channel characteristics of proapoptotic BAX and antiapoptotic BCL-2. Proc Natl Acad Sci USA 1997; 94:11357–11362.PubMedGoogle Scholar
  77. 77.
    Antonsson B, Montessuit S, Lauper S et al. Bax oligomerization is required for channel-forming activity in liposomes and to trigger cytochrome c release from mitochondria. Biochem J 2000; 345(Pt 2):271–278.PubMedGoogle Scholar
  78. 78.
    Karbowski M, Lee YJ, Gaume B et al. Spatial and temporal association of Bax with mitochondrial fission sites, Drp1 and Mfn2 during apoptosis. J Cell Biol 2002; 159:931–938.PubMedGoogle Scholar
  79. 79.
    Han J, Flemington C, Houghton AB et al. Expression of bbc3, a pro-apoptotic BH3-only gene, is regulated by diverse cell death and survival signals. Proc Natl Acad Sci USA 2001; 98:11318–11323.PubMedGoogle Scholar
  80. 80.
    Wu X, Deng Y. Bax and BH3-domain-only proteins in p53-mediated apoptosis. Front Biosci 2002; 7:d151–d156.PubMedGoogle Scholar
  81. 81.
    Mandal M, Crusio KM, Meng F et al. Regulation of lymphocyte progenitor survival by the proapoptotic activities of Bim and Bid. Proc Natl Acad Sci USA 2008; 105:20840–20845.PubMedGoogle Scholar
  82. 82.
    Datta SR, Ranger AM, Lin MZ et al. Survival factor-mediated BAD phosphorylation raises the mitochondrial threshold for apoptosis. Dev Cell 2002; 3:631–643.PubMedGoogle Scholar
  83. 83.
    Datta SR, Katsov A, Hu L et al. 14-3-3 proteins and survival kinases cooperate to inactivate BAD by BH3 domain phosphorylation. Mol Cell 2000; 6:41–51.PubMedGoogle Scholar
  84. 84.
    Desagher S, Osen-Sand A, Nichols A et al. Bid-induced conformational change of Bax is responsible for mitochondrial cytochrome c release during apoptosis. J Cell Biol 1999; 144:891–901.PubMedGoogle Scholar
  85. 85.
    Li H, Zhu H, Xu CJ et al. Cleavage of BID by caspase 8 mediates the mitochondrial damage in the Fas pathway of apoptosis. Cell 1998; 94:491–501.PubMedGoogle Scholar
  86. 86.
    Letai A, Bassik MC, Walensky LD et al. Distinct BH3 domains either sensitize or activate mitochondrial apoptosis, serving as prototype cancer therapeutics. Cancer Cell 2002; 2:183–192.PubMedGoogle Scholar
  87. 87.
    Bereiter-Hahn J, Voth M. Dynamics of mitochondria in living cells: shape changes, dislocations, fusion and fission of mitochondria. Microsc Res Tech 1994; 27:198–219.PubMedGoogle Scholar
  88. 88.
    Frey TG, Mannella CA. The internal structure of mitochondria. Trends Biochem Sci 2000; 25:319–324.PubMedGoogle Scholar
  89. 89.
    Smirnova E, Griparic L, Shurland DL et al. Dynamin-related protein Drp1 is required for mitochondrial division in mammalian cells. Mol Biol Cell 2001; 12:2245–2256.PubMedGoogle Scholar
  90. 90.
    Pitts KR, Yoon Y, Krueger EW et al. The dynamin-like protein DLP1 is essential for normal distribution and morphology of the endoplasmic reticulum and mitochondria in mammalian cells. Mol Biol Cell 1999; 10:4403–4417.PubMedGoogle Scholar
  91. 91.
    James DI, Parone PA, Mattenberger Y et al. hFis1, a novel component of the mammalian mitochondrial fission machinery. J Biol Chem 2003; 278:36373–36379.PubMedGoogle Scholar
  92. 92.
    Cereghetti GM, Stangherlin A, Martins de BO et al. Dephosphorylation by calcineurin regulates translocation of Drp1 to mitochondria. Proc Natl Acad Sci USA 2008; 105:15803–15808.PubMedGoogle Scholar
  93. 93.
    Yoon Y, Krueger EW, Oswald BJ et al. The mitochondrial protein hFis1 regulates mitochondrial fission in mammalian cells through an interaction with the dynamin-like protein DLP1. Mol Cell Biol 2003; 23:5409–5420.PubMedGoogle Scholar
  94. 94.
    Santel A, Fuller MT. Control of mitochondrial morphology by a human mitofusin. J Cell Sci 2001; 114:867–874.PubMedGoogle Scholar
  95. 95.
    Legros F, Lombes A, Frachon P et al. Mitochondrial fusion in human cells is efficient, requires the inner membrane potential and is mediated by mitofusins. Mol Biol Cell 2002; 13:4343–4354.PubMedGoogle Scholar
  96. 96.
    Chen H, McCaffery JM, Chan DC. Mitochondrial Fusion Protects against Neurodegeneration in the Cerebellum. Cell 2007; 130:548–562.PubMedGoogle Scholar
  97. 97.
    Chen H, Detmer SA, Ewald AJ et al. Mitofusins Mfn1 and Mfn2 coordinately regulate mitochondrial fusion and are essential for embryonic development. J Cell Biol 2003; 160:189–200.PubMedGoogle Scholar
  98. 98.
    Akepati VR, Muller EC, Otto A et al. Characterization of OPA1 isoforms isolated from mouse tissues. J Neurochem 2008; 106:372–383.PubMedGoogle Scholar
  99. 99.
    Cipolat S, de Brito OM, Dal Zilio B et al. OPA1 requires mitofusin 1 to promote mitochondrial fusion. Proc Natl Acad Sci USA 2004; 101:15927–15932.PubMedGoogle Scholar
  100. 100.
    Cribbs JT, Strack S. Reversible phosphorylation of Drp1 by cyclic AMP-dependent protein kinase and calcineurin regulates mitochondrial fission and cell death. EMBO Rep 2007; 8:939–944.Google Scholar
  101. 101.
    Chang CR, Blackstone C. Cyclic AMP-dependent protein kinase phosphorylation of Drp1 regulates its GTPase activity and mitochondrial morphology. J Biol Chem 2007; 282:21583–21587.PubMedGoogle Scholar
  102. 102.
    Taguchi N, Ishihara N, Jofuku A et al. Mitotic phosphorylation of dynamin-related GTPase Drp1 participates in mitochondrial fission. J Biol Chem 2007; 282:11521–11529.PubMedGoogle Scholar
  103. 103.
    Harder Z, Zunino R, McBride H. Sumo1 conjugates mitochondrial substrates and participates in mitochondrial fission. Curr Biol 2004; 14:340–345.PubMedGoogle Scholar
  104. 104.
    Wasiak S, Zunino R, McBride HM. Bax/Bak promote sumoylation of DRP1 and its stable association with mitochondria during apoptotic cell death. J Cell Biol 2007; 177:439–450.PubMedGoogle Scholar
  105. 105.
    Anesti V, Scorrano L. The relationship between mitochondrial shape and function and the cytoskeleton. Biochim Biophys Acta 2006; 1757:692–699.PubMedGoogle Scholar
  106. 106.
    Martinou I, Desagher S, Eskes R et al. The release of cytochrome c from mitochondria during apoptosis of NGF-deprived sympathetic neurons is a reversible event. J Cell Biol 1999; 144:883–889.PubMedGoogle Scholar
  107. 107.
    Frank S, Gaume B, Bergmann-Leitner ES et al. The role of dynamin-related protein 1, a mediator of mitochondrial fission, in apoptosis. Dev Cell 2001; 1:515–525.PubMedGoogle Scholar
  108. 108.
    Karbowski M, Arnoult D, Chen H et al. Quantitation of mitochondrial dynamics by photolabeling of individual organelles shows that mitochondrial fusion is blocked during the Bax activation phase of apoptosis. J Cell Biol 2004; 164:493–499.PubMedGoogle Scholar
  109. 109.
    Jahani-Asl A, Cheung EC, Neuspiel M et al. Mitofusin 2 protects cerebellar granule neurons against injury induced cell death. J Biol Chem 2007; 282:23788–23798.PubMedGoogle Scholar
  110. 110.
    Barsoum MJ, Yuan H, Gerencser AA et al. Nitric oxide-induced mitochondrial fission is regulated by dynamin-related GTPases in neurons. EMBO J 2006; 25:3900–3911.PubMedGoogle Scholar
  111. 111.
    Leinninger GM, Backus C, Sastry AM et al. Mitochondria in DRG neurons undergo hyperglycemic mediated injury through Bim, Bax and the fission protein Drp1. Neurobiol Dis 2006; 23:11–22.PubMedGoogle Scholar
  112. 112.
    Yuan H, Gerencser AA, Liot G et al. Mitochondrial fission is an upstream and required event for bax foci formation in response to nitric oxide in cortical neurons. Cell Death Differ 2007; 14:462–471.PubMedGoogle Scholar
  113. 113.
    Dagda RK, Merrill RA, Cribbs JT et al. The spinocerebellar ataxia 12 gene product and protein phosphatase 2A regulatory subunit Bb2 antagonizes neuronal survival by promoting mitochondrial fission. J Biol Chem 2008; 283:36241–36248.PubMedGoogle Scholar
  114. 114.
    Parra V, Eisner V, Chiong M et al. Changes in mitochondrial dynamics during ceramide-induced cardiomyocyte early apoptosis. Cardiovasc Res 2008; 77:387–397.PubMedGoogle Scholar
  115. 115.
    Yu T, Sheu SS, Robotham JL et al. Mitochondrial fission mediates high glucose-induced cell death through elevated production of reactive oxygen species. Cardiovasc Res 2008; 79:341–351.PubMedGoogle Scholar
  116. 116.
    Yu T, Robotham JL, Yoon Y. Increased production of reactive oxygen species in hyperglycemic conditions requires dynamic change of mitochondrial morphology. Proc Natl Acad Sci USA 2006; 103:2653–2658.PubMedGoogle Scholar
  117. 117.
    Parone PA, James DI, Da CS et al. Inhibiting the mitochondrial fission machinery does not prevent Bax/Bak-dependent apoptosis. Mol Cell Biol 2006; 26:7397–7408.PubMedGoogle Scholar
  118. 118.
    Estaquier J, Arnoult D. Inhibiting Drp1-mediated mitochondrial fission selectively prevents the release of cytochrome c during apoptosis. Cell Death Differ 2007; 14:1086–1094.PubMedGoogle Scholar
  119. 119.
    Cassidy-Stone A, Chipuk JE, Ingerman E et al. Chemical inhibition of the mitochondrial division dynamin reveals its role in Bax/Bak-dependent mitochondrial outer membrane permeabilization. Dev Cell 2008; 14:193–204.PubMedGoogle Scholar
  120. 120.
    Jagasia R, Grote P, Westermann B et al. DRP-1-mediated mitochondrial fragmentation during EGL-1-induced cell death in C. elegans. Nature 2005; 433:754–760.PubMedGoogle Scholar
  121. 121.
    Goyal G, Fell B, Sarin A et al. Role of mitochondrial remodeling in programmed cell death in Drosophila melanogaster. Dev Cell 2007; 12:807–816.PubMedGoogle Scholar
  122. 122.
    Sheridan C, Delivani P, Cullen SP et al. Bax-or Bak-induced mitochondrial fission can be uncoupled from cytochrome C release. Mol Cell 2008; 31:570–585.PubMedGoogle Scholar
  123. 123.
    Sugioka R, Shimizu S, Tsujimoto Y. Fzo1, a protein involved in mitochondrial fusion, inhibits apoptosis. J Biol Chem 2004; 279:52726–52734.PubMedGoogle Scholar
  124. 124.
    Frezza C, Cipolat S, Martins dB et al. OPA1 controls apoptotic cristae remodeling independently from mitochondrial fusion. Cell 2006; 126:177–189.PubMedGoogle Scholar
  125. 125.
    Men X, Wang H, Li M et al. Dynamin-related protein 1 mediates high glucose induced pancreatic beta cell apoptosis. Int J Biochem Cell Biol 2009; 41:879–890.PubMedGoogle Scholar
  126. 126.
    Fannjiang Y, Cheng WC, Lee SJ et al. Mitochondrial fission proteins regulate programmed cell death in yeast. Genes Dev 2004; 18:2785–2797.PubMedGoogle Scholar
  127. 127.
    Delivani P, Adrain C, Taylor RC et al. Role for CED-9 and Egl-1 as regulators of mitochondrial fission and fusion dynamics. Mol Cell 2006; 21:761–773.PubMedGoogle Scholar
  128. 128.
    Karbowski M, Norris KL, Cleland MM et al. Role of Bax and Bak in mitochondrial morphogenesis. Nature 2006; 443:658–662.PubMedGoogle Scholar
  129. 129.
    Scorrano L, Ashiya M, Buttle K et al. A distinct pathway remodels mitochondrial cristae and mobilizes cytochrome c during apoptosis. Dev Cell 2002; 2:55–67.PubMedGoogle Scholar
  130. 130.
    Yamaguchi R, Lartigue L, Perkins G et al. Opa1-mediated cristae opening is Bax/Bak and BH3 dependent, required for apoptosis and independent of Bak oligomerization. Mol Cell 2008; 31:557–569.PubMedGoogle Scholar
  131. 131.
    Epand RF, Martinou JC, Fornallaz-Mulhauser M et al. The apoptotic protein tBid promotes leakage by altering membrane curvature. J Biol Chem 2002; 277:32632–32639.PubMedGoogle Scholar

Copyright information

© Landes Bioscience and Springer Science+Business Media 2010

Authors and Affiliations

  1. 1.Department of Cell Physiology and MetabolismUniversity of Geneva Medical SchoolGenèveSwitzerland
  2. 2.Dulbecco-Telethon InstituteVenetian Institute of Molecular MedicinePadovaItaly

Personalised recommendations