Mitochondrial Regulation of Cell Death

  • Dawei Liu
  • Jean-Luc Perfettini
  • Catherine Brenner


Mitochondria are multifaceted organelles exerting vital as well as lethal functions within eukaryotic cells. When fueled with substrates and oxygen, mitochondria govern metabolic pathways, regulate calcium fluxes and are deeply involved in redox homeostasis. In stress conditions, notably when calcium and redox balances are altered, mitochondria sense cellular damages and ultimately, can orchestrate some phylogenetically-conserved forms of cell death such as intrinsic apoptosis, parthanatos as well as mitochondrial permeability transition-mediated necrosis. In contrast, they do not influence other cell death modalities such as necroptosis and ferroptosis. The execution of these mitochondria-dependent lethal processes involves the expression of mitochondria or nucleus-encoded proteins such as BCL-2 family members, VDAC, ANT, cytochrome c, Smac/Diablo, as well as Omi/HtrA2. In addition, mitochondria can also influence the cell fate through fusion/fission of the mitochondrial network and mitophagy to eliminate damaged mitochondria. Here, we will review and discuss basic knowledge on the role of mitochondria in the complex regulation of cell death.


ROS Ant BCL-2 Calcium Energetic metabolism Permeability Transition VDAC 



C.B. is funded by ANR (ANR-13-ISV1-0001-01) and the Investment for the Future program ANR-11-IDEX-0003-01 within the LABEX ANR-10-LABX-0033. D.L. is funded by scholarship from Chine Scientific Council (CSC). This work was supported by funds from Agence Nationale de la Recherche (ANR-10-IBHU-0001, ANR-10-LABX33 and ANR-11-IDEX-003-01), Electricité de France, Fondation Gustave Roussy, Institut National du Cancer (INCA 9414), Cancéropôle Ile de France, NATIXIS, SIDACTION and the French National Agency for Research on AIDS and viral Hepatitis (ANRSH) (to J-L.P.).


  1. Aerts L, De Strooper B, Morais VA (2015) PINK1 activation-turning on a promiscuous kinase. Biochem Soc Trans 43:280–286PubMedCrossRefGoogle Scholar
  2. Bai L, Smith DC, Wang S (2014) Small-molecule SMAC mimetics as new cancer therapeutics. Pharmacol Ther 144:82–95PubMedPubMedCentralCrossRefGoogle Scholar
  3. Balaban RS, Nemoto S, Finkel T (2005) Mitochondria, oxidants, and aging. Cell 120:483–495PubMedCrossRefGoogle Scholar
  4. Baughman JM, Perocchi F, Girgis HS, Plovanich M, Belcher-Timme CA, Sancak Y, Bao XR, Strittmatter L, Goldberger O, Bogorad RL (2011) Integrative genomics identifies MCU as an essential component of the mitochondrial calcium uniporter. Nature 476:341–345PubMedPubMedCentralCrossRefGoogle Scholar
  5. Bellot G, Garcia-Medina R, Gounon P, Chiche J, Roux D, Pouyssegur J, Mazure NM (2009) Hypoxia-induced autophagy is mediated through hypoxia-inducible factor induction of BNIP3 and BNIP3L via their BH3 domains. Mol Cell Biol 29:2570–2581PubMedPubMedCentralCrossRefGoogle Scholar
  6. Belzacq-Casagrande A-S, Martel C, Pertuiset C, Borgne-Sanchez A, Jacotot E, Brenner C (2008) Pharmacological screening and enzymatic assays for apoptosis. Front Biosci 14:3550–3562Google Scholar
  7. Berezhnov AV, Soutar MP, Fedotova EI, Frolova MS, Plun-Favreau H, Zinchenko VP, Abramov AY (2016) Intracellular pH modulates autophagy and mitophagy. J Biol Chem 291:8701–8708PubMedPubMedCentralCrossRefGoogle Scholar
  8. Bianchi P, Kunduzova O, Masini E, Cambon C, Bani D, Raimondi L, Seguelas M-H, Nistri S, Colucci W, Leducq N (2005) Oxidative stress by monoamine oxidase mediates receptor-independent cardiomyocyte apoptosis by serotonin and postischemic myocardial injury. Circulation 112:3297–3305PubMedCrossRefGoogle Scholar
  9. Bossy-Wetzel E, Green DR (1999) Caspases induce cytochrome c release from mitochondria by activating cytosolic factors. J Biol Chem 274:17484–17490PubMedCrossRefGoogle Scholar
  10. Breckenridge DG, Stojanovic M, Marcellus RC, Shore GC (2003) Caspase cleavage product of BAP31 induces mitochondrial fission through endoplasmic reticulum calcium signals, enhancing cytochrome c release to the cytosol. J Cell Biol 160:1115–1127PubMedPubMedCentralCrossRefGoogle Scholar
  11. Brenner C, Kroemer G (2000) Apoptosis mitochondria-the death signal integrators. Science 289:1150–1151PubMedCrossRefGoogle Scholar
  12. Burchell VS, Nelson DE, Sanchez-Martinez A, Delgado-Camprubi M, Ivatt RM, Pogson JH, Randle SJ, Wray S, Lewis PA, Houlden H, Abramov AY, Hardy J, Wood NW, Whitworth AJ, Laman H, Plun-Favreau H (2013) The Parkinson’s disease-linked proteins Fbxo7 and Parkin interact to mediate mitophagy. Nat Neurosci 16:1257–1265PubMedCrossRefGoogle Scholar
  13. Chakrabarti L, Eng J, Ivanov N, Garden GA, La Spada AR (2009) Autophagy activation and enhanced mitophagy characterize the Purkinje cells of pcd mice prior to neuronal death. Mol Brain 2:24PubMedPubMedCentralCrossRefGoogle Scholar
  14. Chen Y, Lewis W, Diwan A, Cheng EH, Matkovich SJ, Dorn GW II (2010) Dual autonomous mitochondrial cell death pathways are activated by nix/BNip3L and induce cardiomyopathy. Proc Natl Acad Sci U S A 107:9035–9042PubMedPubMedCentralCrossRefGoogle Scholar
  15. Chen G, Han Z, Feng D, Chen Y, Chen L, Wu H, Huang L, Zhou C, Cai X, Fu C, Duan L, Wang X, Liu L, Liu X, Shen Y, Zhu Y, Chen Q (2014) A regulatory signaling loop comprising the PGAM5 phosphatase and CK2 controls receptor-mediated mitophagy. Mol Cell 54:362–377PubMedCrossRefGoogle Scholar
  16. Cipolat S, Martins De Brito O, Dal Zilio B, Scorrano L (2004) OPA1 requires mitofusin 1 to promote mitochondrial fusion. Proc Natl Acad Sci U S A 101:15927–15932PubMedPubMedCentralCrossRefGoogle Scholar
  17. Clark IE, Dodson MW, Jiang C, Cao JH, Huh JR, Seol JH, Yoo SJ, Hay BA, Guo M (2006) Drosophila pink1 is required for mitochondrial function and interacts genetically with parkin. Nature 441:1162–1166PubMedCrossRefGoogle Scholar
  18. Clement MV, Pervaiz S (2001) Intracellular superoxide and hydrogen peroxide concentrations: a critical balance that determines survival or death. Redox Rep 6:211–214PubMedCrossRefGoogle Scholar
  19. Cory S, Adams JM (2002) The Bcl2 family: regulators of the cellular life-or-death switch. Nat Rev Cancer 2:647–656PubMedCrossRefGoogle Scholar
  20. Costantini P, Belzacq AS, Vieira HL, Larochette N, De Pablo MA, Zamzami N, Susin SA, Brenner C, Kroemer G (2000) Oxidation of a critical thiol residue of the adenine nucleotide translocator enforces Bcl-2-independent permeability transition pore opening and apoptosis. Oncogene 19:307–314PubMedCrossRefGoogle Scholar
  21. De Stefani D, Raffaello A, Teardo E, Szabò I, Rizzuto R (2011) A forty-kilodalton protein of the inner membrane is the mitochondrial calcium uniporter. Nature 476:336–340PubMedPubMedCentralCrossRefGoogle Scholar
  22. Dechant R, Binda M, Lee SS, Pelet S, Winderickx J, Peter M (2010) Cytosolic pH is a second messenger for glucose and regulates the PKA pathway through V-ATPase. EMBO J 29:2515–2526PubMedPubMedCentralCrossRefGoogle Scholar
  23. Deniaud A, Rossi C, Berquand A, Homand J, Campagna S, Knoll W, Brenner C, Chopineau J (2007) Voltage-dependent anion channel transports calcium ions through biomimetic membranes. Langmuir 23:3898–3905PubMedCrossRefGoogle Scholar
  24. Di Lisa F, Canton M, Menabò R, Kaludercic N, Bernardi P (2007) Mitochondria and cardioprotection. Heart Fail Rev 12:249–260PubMedCrossRefGoogle Scholar
  25. Du C, Fang M, Li Y, Li L, Wang X (2000) Smac, a mitochondrial protein that promotes cytochrome c-dependent caspase activation by eliminating IAP inhibition. Cell 102:33–42PubMedCrossRefGoogle Scholar
  26. Duchen M (2000a) Mitochondria and Ca2+ in cell physiology and pathophysiology. Cell Calcium 28:339–348PubMedCrossRefGoogle Scholar
  27. Duchen MR (2000b) Mitochondria and calcium: from cell signalling to cell death. J Physiol 529:57–68PubMedPubMedCentralCrossRefGoogle Scholar
  28. Elmore S (2007) Apoptosis: a review of programmed cell death. Toxicol Pathol 35:495–516PubMedPubMedCentralCrossRefGoogle Scholar
  29. Ermak G, Sojitra S, Yin F, Cadenas E, Cuervo AM, Davies KJ (2012) Chronic expression of RCAN1-1L protein induces mitochondrial autophagy and metabolic shift from oxidative phosphorylation to glycolysis in neuronal cells. J Biol Chem 287:14088–14098PubMedPubMedCentralCrossRefGoogle Scholar
  30. Eskes R, Antonsson B, Osen-Sand A, Montessuit S, Richter C, Sadoul R, Mazzei G, Nichols A, Martinou J-C (1998) Bax-induced cytochrome C release from mitochondria is independent of the permeability transition pore but highly dependent on Mg2+ ions. J Cell Biol 143:217–224PubMedPubMedCentralCrossRefGoogle Scholar
  31. Galluzzi L, Bravo-San Pedro J, Vitale I, Aaronson S, Abrams J, Adam D, Alnemri E, Altucci L, Andrews D, Annicchiarico-Petruzzelli M (2015) Essential versus accessory aspects of cell death: recommendations of the NCCD 2015. Cell Death Differ 22:58PubMedCrossRefGoogle Scholar
  32. Galluzzi L, Kepp O, Kroemer G (2016) Mitochondrial regulation of cell death: a phylogenetically conserved control. Microbial Cell 3:101–108PubMedPubMedCentralCrossRefGoogle Scholar
  33. Garrido C, Galluzzi L, Brunet M, Puig PE, Didelot C, Kroemer G (2006) Mechanisms of cytochrome c release from mitochondria. Cell Death Differ 13:1423–1433PubMedCrossRefGoogle Scholar
  34. Gegg ME, Cooper JM, Chau KY, Rojo M, Schapira AH, Taanman JW (2010) Mitofusin 1 and mitofusin 2 are ubiquitinated in a PINK1/parkin-dependent manner upon induction of mitophagy. Hum Mol Genet 19:4861–4870PubMedPubMedCentralCrossRefGoogle Scholar
  35. Gincel D, Hilal Z, Shoshan-Barmatz V (2001) Calcium binding and translocation by the voltage-dependent anion channel: a possible regulatory mechanism in mitochondrial function. Biochem J 358:147–155PubMedPubMedCentralCrossRefGoogle Scholar
  36. Ha JY, Kim JS, Kim SE, Son JH (2014) Simultaneous activation of mitophagy and autophagy by staurosporine protects against dopaminergic neuronal cell death. Neurosci Lett 561:101–106PubMedCrossRefGoogle Scholar
  37. Halliwell B (1994) Free radicals, antioxidants, and human disease: curiosity, cause, or consequence? Lancet 344:721–724PubMedCrossRefGoogle Scholar
  38. Halliwell B, Gutteridge JMC (1999) Free radicals in biology and medicine. Clarendon Press, Oxford, EnglandGoogle Scholar
  39. Hanna RA, Quinsay MN, Orogo AM, Giang K, Rikka S, Gustafsson AB (2012) Microtubule-associated protein 1 light chain 3 (LC3) interacts with Bnip3 protein to selectively remove endoplasmic reticulum and mitochondria via autophagy. J Biol Chem 287:19094–19104PubMedPubMedCentralCrossRefGoogle Scholar
  40. Harada H, Becknell B, Wilm M, Mann M, Huang LJ-S, Taylor SS, Scott JD, Korsmeyer SJ (1999) Phosphorylation and inactivation of BAD by mitochondria-anchored protein kinase a. Mol Cell 3:413–422PubMedCrossRefGoogle Scholar
  41. Hegde R, Srinivasula SM, Zhang Z, Wassell R, Mukattash R, Cilenti L, Dubois G, Lazebnik Y, Zervos AS, Fernandes-Alnemri T (2002) Identification of Omi/HtrA2 as a mitochondrial apoptotic serine protease that disrupts inhibitor of apoptosis protein-caspase interaction. J Biol Chem 277:432–438PubMedCrossRefGoogle Scholar
  42. Hermes-Lima M, Castilho RF, Valle VG, Bechara EJ, Vercesi AE (1992) Calcium-dependent mitochondrial oxidative damage promoted by 5-aminolevulinic acid. Biochim Biophys Acta 1180:201–206PubMedCrossRefGoogle Scholar
  43. Ichas F, Jouaville LS, Mazat J-P (1997) Mitochondria are excitable organelles capable of generating and conveying electrical and calcium signals. Cell 89:1145–1153PubMedCrossRefGoogle Scholar
  44. Juhaszova M, Zorov DB, Kim S-H, Pepe S, Fu Q, Fishbein KW, Ziman BD, Wang S, Ytrehus K, Antos CL (2004) Glycogen synthase kinase-3β mediates convergence of protection signaling to inhibit the mitochondrial permeability transition pore. J Clin Investig 113:1535PubMedPubMedCentralCrossRefGoogle Scholar
  45. Kaludercic N, Carpi A, Menabò R, Di Lisa F, Paolocci N (2011) Monoamine oxidases (MAO) in the pathogenesis of heart failure and ischemia/reperfusion injury. Biochim Biophys Acta 1813:1323–1332PubMedCrossRefGoogle Scholar
  46. Kanno T, Sato EF, Muranaka S, Fujita H, Fujiwara T, Utsumi T, Inoue M, Utsumi K (2004) Oxidative stress underlies the mechanism for Ca2+-induced permeability transition of mitochondria. Free Radic Res 38:27–35PubMedCrossRefGoogle Scholar
  47. Kim I, Rodriguez-Enriquez S, Lemasters JJ (2007) Selective degradation of mitochondria by mitophagy. Arch Biochem Biophys 462:245–253PubMedPubMedCentralCrossRefGoogle Scholar
  48. Koyano F, Okatsu K, Kosako H, Tamura Y, Go E, Kimura M, Kimura Y, Tsuchiya H, Yoshihara H, Hirokawa T, Endo T, Fon EA, Trempe JF, Saeki Y, Tanaka K, Matsuda N (2014) Ubiquitin is phosphorylated by PINK1 to activate parkin. Nature 510:162–166PubMedCrossRefGoogle Scholar
  49. Kroemer G, Reed JC (2000) Mitochondrial control of cell death. Nat Med 6:513–519PubMedCrossRefGoogle Scholar
  50. Kroemer G, Galluzzi L, Brenner C (2007) Mitochondrial membrane permeabilization in cell death. Physiol Rev 87:99–163PubMedCrossRefGoogle Scholar
  51. Kuwana T, Mackey MR, Perkins G, Ellisman MH, Latterich M, Schneiter R, Green DR, Newmeyer DD (2002) Bid, Bax, and lipids cooperate to form supramolecular openings in the outer mitochondrial membrane. Cell 111:331–342PubMedCrossRefGoogle Scholar
  52. Lazarou M, Sliter DA, Kane LA, Sarraf SA, Wang C, Burman JL, Sideris DP, Fogel AI, Youle RJ (2015) The ubiquitin kinase PINK1 recruits autophagy receptors to induce mitophagy. Nature 524:309–314PubMedPubMedCentralCrossRefGoogle Scholar
  53. Le Bras M, Clement MV, Pervaiz S, Brenner C (2005) Reactive oxygen species and the mitochondrial signaling pathway of cell death. Histol Histopathol 20:205–220PubMedGoogle Scholar
  54. Lenaz G (2001) The mitochondrial production of reactive oxygen species: mechanisms and implications in human pathology. IUBMB Life 52:159–164PubMedCrossRefGoogle Scholar
  55. Lewis CA, Parker SJ, Fiske BP, Mccloskey D, Gui DY, Green CR, Vokes NI, Feist AM, Vander Heiden MG, Metallo CM (2014) Tracing compartmentalized NADPH metabolism in the cytosol and mitochondria of mammalian cells. Mol Cell 55:253–263PubMedPubMedCentralCrossRefGoogle Scholar
  56. Lin MT, Beal MF (2006) Mitochondrial dysfunction and oxidative stress in neurodegenerative diseases. Nature 443:787–795PubMedCrossRefGoogle Scholar
  57. Liu X, Kim CN, Yang J, Jemmerson R, Wang X (1996) Induction of apoptotic program in cell-free extracts: requirement for dATP and cytochrome c. Cell 86:147–157PubMedCrossRefGoogle Scholar
  58. Liu L, Feng D, Chen G, Chen M, Zheng Q, Song P, Ma Q, Zhu C, Wang R, Qi W, Huang L, Xue P, Li B, Wang X, Jin H, Wang J, Yang F, Liu P, Zhu Y, Sui S, Chen Q (2012) Mitochondrial outer-membrane protein FUNDC1 mediates hypoxia-induced mitophagy in mammalian cells. Nat Cell Biol 14:177–185PubMedCrossRefGoogle Scholar
  59. Liu YQ, Ji Y, Li XZ, Tian KL, Young CY, Lou HX, Yuan HQ (2013) Retigeric acid B-induced mitophagy by oxidative stress attenuates cell death against prostate cancer cells in vitro. Acta Pharmacol Sin 34:1183–1191PubMedPubMedCentralCrossRefGoogle Scholar
  60. Liu L, Sakakibara K, Chen Q, Okamoto K (2014) Receptor-mediated mitophagy in yeast and mammalian systems. Cell Res 24:787–795PubMedPubMedCentralCrossRefGoogle Scholar
  61. Luo X, Budihardjo I, Zou H, Slaughter C, Wang X (1998) Bid, a Bcl2 interacting protein, mediates cytochrome c release from mitochondria in response to activation of cell surface death receptors. Cell 94:481–490PubMedCrossRefGoogle Scholar
  62. Madesh M, Hajnoczky G (2001) VDAC-dependent permeabilization of the outer mitochondrial membrane by superoxide induces rapid and massive cytochrome c release. J Cell Biol 155:1003–1015PubMedPubMedCentralCrossRefGoogle Scholar
  63. Martel C, Allouche M, Esposti D, Fanelli E, Boursier C, Henry C, Chopineau J, Calamita G, Kroemer G, Lemoine A (2012) GSK3-mediated VDAC phosphorylation controls outer mitochondrial membrane permeability during lipid accumulation. Hepatology 57:93–102CrossRefGoogle Scholar
  64. Martinou JC, Green DR (2001) Breaking the mitochondrial barrier. Nat Rev Mol Cell Biol 2:63–67PubMedCrossRefGoogle Scholar
  65. Martins LM, Iaccarino I, Tenev T, Gschmeissner S, Totty NF, Lemoine NR, Savopoulos J, Gray CW, Creasy CL, Dingwall C (2002) The serine protease Omi/HtrA2 regulates apoptosis by binding XIAP through a reaper-like motif. J Biol Chem 277:439–444PubMedCrossRefGoogle Scholar
  66. Martins I, Raza SQ, Voisin L, Dakhli H, Law F, Allouch A, Thoreau M, Brenner C, Deutsch E, Perfettini J-L (2017) Entosis: the emerging face of non-cell-autonomous type IV programmed death. Biomed J 40(3):133–140PubMedCrossRefGoogle Scholar
  67. Marzo I, Brenner C, Zamzami N, Jurgensmeier JM, Susin SA, Vieira HL, Prevost MC, Xie Z, Matsuyama S, Reed JC, Kroemer G (1998) Bax and adenine nucleotide translocator cooperate in the mitochondrial control of apoptosis. Science 281:2027–2031PubMedCrossRefGoogle Scholar
  68. Mattson MP, Chan SL (2003) Calcium orchestrates apoptosis. Nat Cell Biol 5:1041–1043PubMedCrossRefGoogle Scholar
  69. Morais VA, Verstreken P, Roethig A, Smet J, Snellinx A, Vanbrabant M, Haddad D, Frezza C, Mandemakers W, Vogt-Weisenhorn D, Van Coster R, Wurst W, Scorrano L, De Strooper B (2009) Parkinson’s disease mutations in PINK1 result in decreased complex I activity and deficient synaptic function. EMBO Mol Med 1:99–111PubMedPubMedCentralCrossRefGoogle Scholar
  70. Murphy MP, Holmgren A, Larsson N-G, Halliwell B, Chang CJ, Kalyanaraman B, Rhee SG, Thornalley PJ, Partridge L, Gems D (2011) Unraveling the biological roles of reactive oxygen species. Cell Metab 13:361–366PubMedPubMedCentralCrossRefGoogle Scholar
  71. Neupert W (1997) Protein import into mitochondria. Annu Rev Biochem 66:863–917PubMedCrossRefGoogle Scholar
  72. Novak I, Kirkin V, Mcewan DG, Zhang J, Wild P, Rozenknop A, Rogov V, Lohr F, Popovic D, Occhipinti A, Reichert AS, Terzic J, Dotsch V, Ney PA, Dikic I (2010) Nix is a selective autophagy receptor for mitochondrial clearance. EMBO Rep 11:45–51PubMedCrossRefGoogle Scholar
  73. Orrenius S, Zhivotovsky B (2005) Cardiolipin oxidation sets cytochrome c free. Nat Chem Biol 1:188–189PubMedCrossRefGoogle Scholar
  74. Pan X, Liu J, Nguyen T, Liu C, Sun J, Teng Y, Fergusson MM, Rovira II, Allen M, Springer DA (2013) The physiological role of mitochondrial calcium revealed by mice lacking the mitochondrial calcium uniporter. Nat Cell Biol 15:1464–1472PubMedPubMedCentralCrossRefGoogle Scholar
  75. Patterson S, Spahr C, Daugas E, Susin S, Irinopoulou T, Koehler C, Kroemer G (2000) Mass spectrometric identification of proteins released from mitochondria undergoing permeability transition. Cell Death Differ 7:137PubMedCrossRefGoogle Scholar
  76. Pchejetski D, Kunduzova O, Dayon A, Calise D, Seguelas M-H, Leducq N, Seif I, Parini A, Cuvillier O (2007) Oxidative stress-dependent sphingosine kinase-1 inhibition mediates monoamine oxidase A-associated cardiac cell apoptosis. Circ Res 100:41–49PubMedCrossRefGoogle Scholar
  77. Petit PX, Goubern M, Diolez P, Susin SA, Zamzami N, Kroemer G (1998) Disruption of the outer mitochondrial membrane as a result of large amplitude swelling: the impact of irreversible permeability transition. FEBS Lett 426:111–116PubMedCrossRefGoogle Scholar
  78. Pozzan T, Rizzuto R, Volpe P, Meldolesi J (1994) Molecular and cellular physiology of intracellular calcium stores. Physiol Rev 74:595–637PubMedCrossRefGoogle Scholar
  79. Reed JC (2000) Mechanisms of apoptosis. Am J Pathol 157:1415–1430PubMedPubMedCentralCrossRefGoogle Scholar
  80. Rikka S, Quinsay MN, Thomas RL, Kubli DA, Zhang X, Murphy AN, Gustafsson AB (2011) Bnip3 impairs mitochondrial bioenergetics and stimulates mitochondrial turnover. Cell Death Differ 18:721–731PubMedCrossRefGoogle Scholar
  81. Rodriguez-Enriquez S, He L, Lemasters JJ (2004) Role of mitochondrial permeability transition pores in mitochondrial autophagy. Int J Biochem Cell Biol 36:2463–2472PubMedCrossRefGoogle Scholar
  82. Schwarten M, Mohrlüder J, Ma P, Stoldt M, Thielmann Y, Stangler T, Hersch N, Hoffmann B, Merkel R, Willbold D (2014) Nix directly binds to GABARAP: a possible crosstalk between apoptosis and autophagy. Autophagy 5:690–698CrossRefGoogle Scholar
  83. Shi RY, Zhu SH, Li V, Gibson SB, Xu XS, Kong JM (2014) BNIP3 interacting with LC3 triggers excessive mitophagy in delayed neuronal death in stroke. CNS Neurosci Ther 20:1045–1055PubMedCrossRefGoogle Scholar
  84. Susin SA, Zamzami N, Castedo M, Hirsch T, Marchetti P, Macho A, Daugas E, Geuskens M, Kroemer G (1996) Bcl-2 inhibits the mitochondrial release of an apoptogenic protease. J Exp Med 184:1331–1341PubMedCrossRefGoogle Scholar
  85. Tanaka A, Cleland MM, Xu S, Narendra DP, Suen DF, Karbowski M, Youle RJ (2010) Proteasome and p97 mediate mitophagy and degradation of mitofusins induced by Parkin. J Cell Biol 191:1367–1380PubMedPubMedCentralCrossRefGoogle Scholar
  86. Tomasello F, Messina A, Lartigue L, Schembri L, Medina C, Reina S, Thoraval D, Crouzet M, Ichas F, De Pinto V (2009) Outer membrane VDAC1 controls permeability transition of the inner mitochondrial membrane in cellulo during stress-induced apoptosis. Cell Res 19:1363PubMedCrossRefGoogle Scholar
  87. Tsujimoto Y, Cossman J, Jaffe E, Croce CM (1985) Involvement of the bcl-2 gene in human follicular lymphoma. Science 228:1440–1444PubMedCrossRefGoogle Scholar
  88. Van Loo G, Van Gurp M, Depuydt B, Srinivasula SM, Rodriguez I, Alnemri ES, Gevaert K, Vandekerckhove J, Declercq W, Vandenabeele P (2002) The serine protease Omi/HtrA2 is released from mitochondria during apoptosis. Omi interacts with caspase-inhibitor XIAP and induces enhanced caspase activity. Cell Death Differ 9:20–26PubMedCrossRefGoogle Scholar
  89. Vaseva AV, Marchenko ND, Ji K, Tsirka SE, Holzmann S, Moll UM (2012) p53 opens the mitochondrial permeability transition pore to trigger necrosis. Cell 149:1536–1548PubMedPubMedCentralCrossRefGoogle Scholar
  90. Vieira H, Belzacq A-S, Haouzi D, Bernassola F, Cohen I, Jacotot E, Ferri KF, El Hamel C, Bartle LM, Melino G (2001) The adenine nucleotide translocator: a target of nitric oxide, peroxynitrite, and 4-hydroxynonenal. Oncogene 20:4305–4316PubMedCrossRefGoogle Scholar
  91. Wang S, He M, Li L, Liang Z, Zou Z, Tao A (2016) Cell-in-cell death is not restricted by caspase-3 deficiency in MCF-7 cells. J Breast Cancer 19:231–241PubMedPubMedCentralCrossRefGoogle Scholar
  92. Wang Z, Figueiredo-Pereira C, Oudot C, Vieira H, Brenner C (2017) Mitochondrion: a common organelle for distinct cell deaths? Int Rev Cell Mol Biol 331:245–287PubMedCrossRefGoogle Scholar
  93. Wei MC, Zong W-X, Cheng EH-Y, Lindsten T, Panoutsakopoulou V, Ross AJ, Roth KA, Macgregor GR, Thompson CB, Korsmeyer SJ (2001) Proapoptotic BAX and BAK: a requisite gateway to mitochondrial dysfunction and death. Science 292:727–730PubMedPubMedCentralCrossRefGoogle Scholar
  94. Wong E, Cuervo AM (2010) Autophagy gone awry in neurodegenerative diseases. Nat Neurosci 13:805–811PubMedPubMedCentralCrossRefGoogle Scholar
  95. Wu W, Tian W, Hu Z, Chen G, Huang L, Li W, Zhang X, Xue P, Zhou C, Liu L, Zhu Y, Zhang X, Li L, Zhang L, Sui S, Zhao B, Feng D (2014) ULK1 translocates to mitochondria and phosphorylates FUNDC1 to regulate mitophagy. EMBO Rep 15:566–575PubMedPubMedCentralCrossRefGoogle Scholar
  96. Xia M, Meng G, Jiang A, Chen A, Dahlhaus M, Gonzalez P, Beltinger C, Wei J (2014) Mitophagy switches cell death from apoptosis to necrosis in NSCLC cells treated with oncolytic measles virus. Oncotarget 5:3907PubMedPubMedCentralCrossRefGoogle Scholar
  97. Yang Y, Gehrke S, Imai Y, Huang Z, Ouyang Y, Wang JW, Yang L, Beal MF, Vogel H, Lu B (2006) Mitochondrial pathology and muscle and dopaminergic neuron degeneration caused by inactivation of drosophila Pink1 is rescued by Parkin. Proc Natl Acad Sci U S A 103:10793–10798PubMedPubMedCentralCrossRefGoogle Scholar
  98. 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 23:5409–5420PubMedPubMedCentralCrossRefGoogle Scholar
  99. Zamzami N, Kroemer G (2001) The mitochondrion in apoptosis: how Pandora’s box opens. Nat Rev Mol Cell Biol 2:67–71PubMedCrossRefGoogle Scholar
  100. Zamzami N, Marchetti P, Castedo M, Zanin C, Vayssière J-L, Petit PX, Kroemer G (1995) Reduction in mitochondrial potential constitutes an early irreversible step of programmed lymphocyte death in vivo. J Exp Med 181:1661–1672PubMedCrossRefGoogle Scholar
  101. Zhu Y, Massen S, Terenzio M, Lang V, Chen-Lindner S, Eils R, Novak I, Dikic I, Hamacher-Brady A, Brady NR (2013) Modulation of serines 17 and 24 in the LC3-interacting region of Bnip3 determines pro-survival mitophagy versus apoptosis. J Biol Chem 288:1099–1113PubMedCrossRefGoogle Scholar
  102. Zorov DB, Filburn CR, Klotz L-O, Zweier JL, Sollott SJ (2000) Reactive oxygen species (ROS-induced) ROS release. J Exp Med 192:1001–1014PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Dawei Liu
    • 1
  • Jean-Luc Perfettini
    • 2
    • 3
    • 4
  • Catherine Brenner
    • 1
  1. 1.INSERM UMR-S 1180-LabEx LERMITUniversité Paris-Sud, Université Paris-SaclayChâtenay MalabryFrance
  2. 2.Cell Death and Aging TeamGustave RoussyVillejuifFrance
  3. 3.Laboratory of Molecular Radiotherapy, INSERM U1030Gustave RoussyVillejuifFrance
  4. 4.Université Paris Sud - Paris SaclayVillejuifFrance

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