Mitochondrial p53 mediates a transcription-independent regulation of cell respiration and interacts with the mitochondrial F1F0-ATP synthase

Cell Cycle

Volumn 12, Issue 17, 2013, Pages 3781-3793

  Bergeaud, Marie ^a   Mathieu, Lise ^a   Guillaume, Arnaud ^a   Moll, Ute M ^b   Mignotte, Bernard ^a   Le Floch, Nathalie ^a   Vayssière, Jean Luc ^a   Rincheval, Vincent ^a  

^a LABORATOIRE DES SCIENCES DU CLIMAT ET DE L ENVIRONNEMENT   (France)

^b STONY BROOK UNIVERSITY   (United States)

Author keywords

Cancer; Energetic metabo lism; Mitochondria; OSCP; Oxi dative phosphorylation; P53; Reactive oxygen species; Respiration; Tumor suppressor

Indexed keywords

OLIGOMYCIN SENSITIVITY CONFERRING PROTEIN; PROTEIN P53; PROTON TRANSPORTING ADENOSINE TRIPHOSPHATE SYNTHASE; SUPEROXIDE; UNCLASSIFIED DRUG;

ARTICLE; CELL RESPIRATION; CHEMOSENSITIVITY; CONCENTRATION (PARAMETERS); CONTROLLED STUDY; HUMAN; HUMAN CELL; IMMUNOPRECIPITATION; MASS SPECTROMETRY; MITOCHONDRIAL MEMBRANE; MITOCHONDRIAL RESPIRATION; MITOCHONDRION; OXYGEN CONSUMPTION; PROTEIN ASSEMBLY; PROTEIN FUNCTION; PROTEIN LOCALIZATION; PROTEIN PROTEIN INTERACTION; TRANSCRIPTION REGULATION;

EID: 84883585280     PISSN: 15384101     EISSN: 15514005     Source Type: Journal    
DOI: 10.4161/cc.25870     Document Type: Article

References (83)

1. Hollstein M, Sidransky D, Vogelstein B, Harris CC. p53 mutations in human cancers. Science 1991; 253:49-53; PMID:1905840; http://dx.doi.org/10.1126/ science.1905840
2. Fields S, Jang SK. Presence of a potent transcription activating sequence in the p53 protein. Science 1990; 249:1046-9; PMID:2144363; http://dx.doi.org/10.1126/science.2144363
3. Raycroft L, Wu HY, Lozano G. Transcriptional activation by wild-type but not transforming mutants of the p53 anti-oncogene. Science 1990; 249:1049-51; PMID:2144364; http://dx.doi.org/10.1126/science.2144364
4. Weintraub H, Hauschka S, Tapscott SJ. The MCK enhancer contains a p53 responsive element. Proc Natl Acad Sci U S A 1991; 88:4570-1; PMID:1647009; http://dx.doi.org/10.1073/pnas.88.11.4570
5. el-Deiry WS, Kern SE, Pietenpol JA, Kinzler KW, Vogelstein B. Definition of a consensus binding site for p 53. Nat Genet 1992; 1:45-9; PMID:1301998; http://dx.doi.org/10.1038/ng0492-45
6. Maltzman W, Czyzyk L. UV irradiation stimulates levels of p53 cellular tumor antigen in nontransformed mouse cells. Mol Cell Biol 1984; 4:1689-94; PMID:6092932
7. Tishler RB, Calderwood SK, Coleman CN, Price BD. Increases in sequence specific DNA binding by p53 following treatment with chemotherapeutic and DNA damaging agents. Cancer Res 1993; 53(Suppl):2212-6; PMID:8485705
8. Nakamura Y. Isolation of p53-target genes and their functional analysis. Cancer Sci 2004; 95:7-11; PMID:14720320; http://dx.doi.org/10.1111/j.1349-7006. 2004.tb03163.x
9. Riley T, Sontag E, Chen P, Levine A. Transcriptional control of human p53-regulated genes. Nat Rev Mol Cell Biol 2008; 9:402-12; PMID:18431400; http://dx.doi.org/10.1038/nrm2395
10. Wang B, Xiao Z, Ko HL, Ren EC. The p53 response element and transcriptional repression. Cell Cycle 2010; 9:870-9; PMID:20160511; http://dx.doi.org/10.4161/cc.9.5.10825
11. Zuckerman V, Wolyniec K, Sionov RV, Haupt S, Haupt Y. Tumour suppression by p53: the importance of apoptosis and cellular senescence. J Pathol 2009; 219:3-15; PMID:19562738
12. Caelles C, Helmberg A, Karin M. p53-dependent apoptosis in the absence of transcriptional activation of p53-target genes. Nature 1994; 370:220-3; PMID:8028670; http://dx.doi.org/10.1038/370220a0
13. Gottlieb E, Lindner S, Oren M. Relationship of sequence-specific transactivation and p53-regulated apoptosis in interleukin 3-dependent hematopoietic cells. Cell Growth Differ 1996; 7:301-10; PMID:8838860
14. Bissonnette N, Wasylyk B, Hunting DJ. The apoptotic and transcriptional transactivation activities of p53 can be dissociated. Biochem Cell Biol 1997; 75:351-8; PMID:9493957; http://dx.doi.org/10.1139/o97-058
15. Yan Y, Shay JW, Wright WE, Mumby MC. Inhibition of protein phosphatase activity induces p53-dependent apoptosis in the absence of p53 transactivation. J Biol Chem 1997; 272:15220-6; PMID:9182545; http://dx.doi.org/10.1074/jbc.272. 24.15220
16. Haupt Y, Rowan S, Shaulian E, Vousden KH, Oren M. Induction of apoptosis in HeLa cells by transactivation-deficient p53. Genes Dev 1995; 9:2170-83; PMID:7657168; http://dx.doi.org/10.1101/gad.9.17.2170
17. Haupt Y, Rowan S, Shaulian E, Kazaz A, Vousden K, Oren M. p53 mediated apoptosis in HeLa cells: transcription dependent and independent mechanisms. Leukemia 1997; 11(Suppl 3):337-9; PMID:9209383
18. Chen X, Ko LJ, Jayaraman L, Prives C. p53 levels, functional domains, and DNA damage determine the extent of the apoptotic response of tumor cells. Genes Dev 1996; 10:2438-51; PMID:8843196; http://dx.doi.org/10.1101/gad.10.19.2438
19. Marchenko ND, Zaika A, Moll UM. Death signalinduced localization of p53 protein to mitochondria. A potential role in apoptotic signaling. J Biol Chem 2000; 275:16202-12; PMID:10821866; http://dx.doi.org/10.1074/jbc.275.21.16202
20. Mihara M, Erster S, Zaika A, Petrenko O, Chittenden T, Pancoska P, Moll UM. p53 has a direct apoptogenic role at the mitochondria. Mol Cell 2003; 11:577-90; PMID:12667443; http://dx.doi.org/10.1016/S1097-2765(03)00050-9
21. Erster S, Mihara M, Kim RH, Petrenko O, Moll UM. In vivo mitochondrial p53 translocation triggers a rapid first wave of cell death in response to DNA damage that can precede p53 target gene activation. Mol Cell Biol 2004; 24:6728-41; PMID:15254240; http://dx.doi.org/10.1128/MCB.24.15.6728-6741.2004
22. Zhao Y, Chaiswing L, Velez JM, Batinic-Haberle I, Colburn NH, Oberley TD, St Clair DK. p53 translocation to mitochondria precedes its nuclear translocation and targets mitochondrial oxidative defense protein-manganese superoxide dismutase. Cancer Res 2005; 65:3745-50; PMID:15867370; http://dx.doi.org/10.1158/0008-5472.CAN-04-3835
23. Leu JI, Dumont P, Hafey M, Murphy ME, George DL. Mitochondrial p53 activates Bak and causes disruption of a Bak-Mcl1 complex. Nat Cell Biol 2004; 6:443-50; PMID:15077116; http://dx.doi.org/10.1038/ncb1123
24. Chipuk JE, Kuwana T, Bouchier-Hayes L, Droin NM, Newmeyer DD, Schuler M, Green DR. Direct activation of Bax by p53 mediates mitochondrial membrane permeabilization and apoptosis. Science 2004; 303:1010-4; PMID:14963330; http://dx.doi.org/10.1126/science.1092734
25. Deng X, Gao F, Flagg T, Anderson J, May WS. Bcl2's flexible loop domain regulates p53 binding and survival. Mol Cell Biol 2006; 26:4421-34; PMID:16738310; http://dx.doi.org/10.1128/MCB.01647-05
26. Vaseva AV, Moll UM. The mitochondrial p53 pathway. Biochim Biophys Acta 2009; 1787:414-20; PMID:19007744; http://dx.doi.org/10.1016/j.bbabio.2008.10.005
27. Sot B, Freund SM, Fersht AR. Comparative biophysical characterization of p53 with the pro-apoptotic BAK and the anti-apoptotic BCL-xL. J Biol Chem 2007; 282:29193-200; PMID:17699158; http://dx.doi.org/10.1074/jbc.M705544200
28. Tomita Y, Marchenko N, Erster S, Nemajerova A, Dehner A, Klein C, Pan H, Kessler H, Pancoska P, Moll UM. WT p53, but not tumor-derived mutants, bind to Bcl2 via the DNA binding domain and induce mitochondrial permeabilization. J Biol Chem 2006; 281:8600-6; PMID:16443602; http://dx.doi.org/10.1074/jbc. M507611200
29. Petros AM, Gunasekera A, Xu N, Olejniczak ET, Fesik SW. Defining the p53 DNA-binding domain/Bcl-x(L)-binding interface using NMR. FEBS Lett 2004; 559:171-4; PMID:14960327; http://dx.doi.org/10.1016/S0014-5793(04)00059-6
30. Pietsch EC, Perchiniak E, Canutescu AA, Wang G, Dunbrack RL, Murphy ME. Oligomerization of BAK by p53 utilizes conserved residues of the p53 DNA binding domain. J Biol Chem 2008; 283:21294-304; PMID:18524770; http://dx.doi.org/10. 1074/jbc. M710539200
31. Vousden KH, Prives C. Blinded by the Light: The Growing Complexity of p53. Cell 2009; 137:413-31; PMID:19410540; http://dx.doi.org/10.1016/j.cell. 2009.04.037
32. Vousden KH, Ryan KM. p53 and metabolism. Nat Rev Cancer 2009; 9:691-700; PMID:19759539; http://dx.doi.org/10.1038/nrc2715
33. Matoba S, Kang JG, Patino WD, Wragg A, Boehm M, Gavrilova O, Hurley PJ, Bunz F, Hwang PM. p53 regulates mitochondrial respiration. Science 2006; 312:1650-3; PMID:16728594; http://dx.doi.org/10.1126/science.1126863
34. Warburg O. On respiratory impairment in cancer cells. Science 1956; 124:269-70; PMID:13351639
35. Schwartzenberg-Bar-Yoseph F, Armoni M, Karnieli E. The tumor suppressor p53 down-regulates glucose transporters GLUT1 and GLUT4 gene expression. Cancer Res 2004; 64:2627-33; PMID:15059920; http://dx.doi.org/10.1158/0008-5472.CAN-03- 0846
36. Kawauchi K, Araki K, Tobiume K, Tanaka N. p53 regulates glucose metabolism through an IKK-NFkappaB pathway and inhibits cell transformation. Nat Cell Biol 2008; 10:611-8; PMID:18391940; http://dx.doi.org/10.1038/ncb1724
37. Bensaad K, Tsuruta A, Selak MA, Vidal MN, Nakano K, Bartrons R, Gottlieb E, Vousden KH. TIGAR, a p53-inducible regulator of glycolysis and apoptosis. Cell 2006; 126:107-20; PMID:16839880; http://dx.doi.org/10.1016/j.cell.2006.05. 036
38. Tan M, Li S, Swaroop M, Guan K, Oberley LW, Sun Y. Transcriptional activation of the human glutathione peroxidase promoter by p53. J Biol Chem 1999; 274:12061-6; PMID:10207030; http://dx.doi.org/10.1074/jbc.274.17.12061
39. Hussain SP, Amstad P, He P, Robles A, Lupold S, Kaneko I, Ichimiya M, Sengupta S, Mechanic L, Okamura S, et al. p53-induced up-regulation of MnSOD and GPx but not catalase increases oxidative stress and apoptosis. Cancer Res 2004; 64:2350-6; PMID:15059885; http://dx.doi.org/10.1158/0008-5472.CAN-2287-2
40. Sablina AA, Budanov AV, Ilyinskaya GV, Agapova LS, Kravchenko JE, Chumakov PM. The antioxidant function of the p53 tumor suppressor. Nat Med 2005; 11:1306-13; PMID:16286925; http://dx.doi.org/10.1038/nm1320
41. O'Connor JC, Wallace DM, O'Brien CJ, Cotter TG. A novel antioxidant function for the tumorsuppressor gene p53 in the retinal ganglion cell. Invest Ophthalmol Vis Sci 2008; 49:4237-44; PMID:18487368; http://dx.doi.org/10.1167/ iovs.08-1963
42. Velasco-Miguel S, Buckbinder L, Jean P, Gelbert L, Talbott R, Laidlaw J, Seizinger B, Kley N. PA26, a novel target of the p53 tumor suppressor and member of the GADD family of DNA damage and growth arrest inducible genes. Oncogene 1999; 18:127-37; PMID:9926927; http://dx.doi.org/10.1038/sj.onc.1202274
43. Budanov AV, Shoshani T, Faerman A, Zelin E, Kamer I, Kalinski H, Gorodin S, Fishman A, Chajut A, Einat P, et al. Identification of a novel stress-responsive gene Hi95 involved in regulation of cell viability. Oncogene 2002; 21:6017-31; PMID:12203114; http://dx.doi.org/10.1038/sj.onc.1205877
44. Polyak K, Xia Y, Zweier JL, Kinzler KW, Vogelstein B. A model for p53-induced apoptosis. Nature 1997; 389:300-5; PMID:9305847; http://dx.doi.org/10.1038/38525
45. Rivera A, Maxwell SA. The p53-induced gene-6 (proline oxidase) mediates apoptosis through a calcineurin-dependent pathway. J Biol Chem 2005; 280:29346-54; PMID:15914462; http://dx.doi.org/10.1074/jbc.M504852200
46. Liu G, Chen X. The ferredoxin reductase gene is regulated by the p53 family and sensitizes cells to oxidative stress-induced apoptosis. Oncogene 2002; 21:7195-204; PMID:12370809; http://dx.doi.org/10.1038/sj.onc.1205862
47. Dhar SK, Xu Y, St Clair DK. Nuclear factor kappaB-and specificity protein 1-dependent p53-mediated bi-directional regulation of the human manganese superoxide dismutase gene. J Biol Chem 2010; 285:9835-46; PMID:20061391; http://dx.doi.org/10.1074/jbc.M109.060715
48. de Souza-Pinto NC, Harris CC, Bohr VA. p53 functions in the incorporation step in DNA base excision repair in mouse liver mitochondria. Oncogene 2004; 23:6559-68; PMID:15208669; http://dx.doi.org/10.1038/sj.onc.1207874
49. Chen D, Yu Z, Zhu Z, Lopez CD. The p53 pathway promotes efficient mitochondrial DNA base excision repair in colorectal cancer cells. Cancer Res 2006; 66:3485-94; PMID:16585172; http://dx.doi.org/10.1158/0008-5472.CAN-05-4103
50. Lebedeva MA, Eaton JS, Shadel GS. Loss of p53 causes mitochondrial DNA depletion and altered mitochondrial reactive oxygen species homeostasis. Biochim Biophys Acta 2009; 1787:328-34; PMID:19413947; http://dx.doi.org/10.1016/j. bbabio.2009.01.004
51. Kulawiec M, Ayyasamy V, Singh KK. p53 regulates mtDNA copy number and mitocheckpoint pathway. J Carcinog 2009; 8:8; PMID:19439913; http://dx.doi.org/10.4103/1477-3163.50893
52. Park JY, Wang PY, Matsumoto T, Sung HJ, Ma W, Choi JW, Anderson SA, Leary SC, Balaban RS, Kang JG, et al. p53 improves aerobic exercise capacity and augments skeletal muscle mitochondrial DNA content. Circ Res 2009; 105:705-12, 11, 712; PMID:19696408; http://dx.doi.org/10.1161/CIRCRESAHA.109.205310
53. Mahyar-Roemer M, Fritzsche C, Wagner S, Laue M, Roemer K. Mitochondrial p53 levels parallel total p53 levels independent of stress response in human colorectal carcinoma and glioblastoma cells. Oncogene 2004; 23:6226-36; PMID:15247902; http://dx.doi.org/10.1038/sj.onc.1207637
54. Ferecatu I, Bergeaud M, Rodríguez-Enfedaque A, Le Floch N, Oliver L, Rincheval V, Renaud F, Vallette FM, Mignotte B, Vayssière JL. Mitochondrial localization of the low level p53 protein in proliferative cells. Biochem Biophys Res Commun 2009; 387:772-7; PMID:19635458; http://dx.doi.org/10. 1016/j.bbrc.2009.07.111
55. De S, Kumari J, Mudgal R, Modi P, Gupta S, Futami K, Goto H, Lindor NM, Furuichi Y, Mohanty D, et al. RECQL4 is essential for the transport of p53 to mitochondria in normal human cells in the absence of exogenous stress. J Cell Sci 2012; 125:2509-22; PMID:22357944; http://dx.doi.org/10.1242/jcs.101501
56. Burden DA, Osheroff N. Mechanism of action of eukaryotic topoisomerase II and drugs targeted to the enzyme. Biochim Biophys Acta 1998; 1400:139-54; PMID:9748545; http://dx.doi.org/10.1016/S0167-4781(98)00132-8
57. Ono H, Gruhler A, Stuart RA, Guiard B, Schwarz E, Neupert W. Sorting of cytochrome b2 to the intermembrane space of mitochondria. Kinetic analysis of intermediates demonstrates passage through the matrix. J Biol Chem 1995; 270:16932-8; PMID:7622511
58. Hu W, Zhang C, Wu R, Sun Y, Levine A, Feng Z. Glutaminase 2, a novel p53 target gene regulating energy metabolism and antioxidant function. Proc Natl Acad Sci U S A 2010; 107:7455-60; PMID:20378837; http://dx.doi.org/10.1073/pnas. 1001006107
59. Rubinstein J, Walker J. ATP synthase from Saccharomyces cerevisiae: location of the OSCP subunit in the peripheral stalk region. J Mol Biol 2002; 321:613-9; PMID:12206777; http://dx.doi.org/10.1016/S0022-2836(02)00671-X
60. De S, Kumari J, Mudgal R, Modi P, Gupta S, Futami K, Goto H, Lindor NM, Furuichi Y, Mohanty D, et al. RECQL4 is essential for the transport of p53 to mitochondria in normal human cells in the absence of exogenous stress. J Cell Sci 2012; 125:2509-22; PMID:22357944; http://dx.doi.org/10.1242/jcs.101501
61. Yoshida Y, Izumi H, Torigoe T, Ishiguchi H, Itoh H, Kang D, Kohno K. P53 physically interacts with mitochondrial transcription factor A and differentially regulates binding to damaged DNA. Cancer Res 2003; 63:3729-34; PMID:12839966
62. Achanta G, Sasaki R, Feng L, Carew JS, Lu W, Pelicano H, Keating MJ, Huang P. Novel role of p53 in maintaining mitochondrial genetic stability through interaction with DNA Pol gamma. EMBO J 2005; 24:3482-92; PMID:16163384; http://dx.doi.org/10.1038/sj.emboj.7600819
63. Bakhanashvili M, Grinberg S, Bonda E, Rahav G. Excision of nucleoside analogs in mitochondria by p53 protein. AIDS 2009; 23:779-88; PMID:19287302; http://dx.doi.org/10.1097/QAD.0b013e328329c74e
64. Vaseva AV, Marchenko ND, Ji K, Tsirka SE, Holzmann S, Moll UM. p53 opens the mitochondrial permeability transition pore to trigger necrosis. Cell 2012; 149:1536-48; PMID:22726440; http://dx.doi.org/10.1016/j.cell.2012.05.014
65. Lee J, Kim CH, Simon DK, Aminova LR, Andreyev AY, Kushnareva YE, Murphy AN, Lonze BE, Kim KS, Ginty DD, et al. Mitochondrial cyclic AMP response element-binding protein (CREB) mediates mitochondrial gene expression and neuronal survival. J Biol Chem 2005; 280:40398-401; PMID:16207717; http://dx.doi.org/10.1074/jbc.C500140200
66. Cogswell PC, Kashatus DF, Keifer JA, Guttridge DC, Reuther JY, Bristow C, Roy S, Nicholson DW, Baldwin AS Jr. NF-kappa B and I kappa B alpha are found in the mitochondria. Evidence for regulation of mitochondrial gene expression by NF-kappa B. J Biol Chem 2003; 278:2963-8; PMID:12433922; http://dx.doi.org/10. 1074/jbc.M209995200
67. Wegrzyn J, Potla R, Chwae YJ, Sepuri NB, Zhang Q, Koeck T, Derecka M, Szczepanek K, Szelag M, Gornicka A, et al. Function of mitochondrial Stat3 in cellular respiration. Science 2009; 323:793-7; PMID:19131594; http://dx.doi.org/10.1126/science.1164551
68. Ahn BY, Trinh DL, Zajchowski LD, Lee B, Elwi AN, Kim SW. Tid1 is a new regulator of p53 mitochondrial translocation and apoptosis in cancer. Oncogene 2010; 29:1155-66; PMID:19935715; http://dx.doi.org/10.1038/onc.2009.413
69. Hu J, Yao H, Gan F, Tokarski A, Wang Y. Interaction of OKL38 and p53 in regulating mitochondrial structure and function. PLoS One 2012; 7:e43362; PMID:22912861; http://dx.doi.org/10.1371/journal.pone.0043362
70. Tammineni P, Anugula C, Mohammed F, Anjaneyulu M, Larner AC, Sepuri NB. The import of the transcription factor STAT3 into mitochondria depends on GRIM-19, a component of the electron transport chain. J Biol Chem 2013; 288:4723-32; PMID:23271731; http://dx.doi.org/10.1074/jbc. M112.378984
71. Herrmann JM, Riemer J. Mitochondrial disulfide relay: redox-regulated protein import into the intermembrane space. J Biol Chem 2012; 287:4426-33; PMID:22157015; http://dx.doi.org/10.1074/jbc. R111.270678
72. Hainaut P, Mann K. Zinc binding and redox control of p53 structure and function. Antioxid Redox Signal 2001; 3:611-23; PMID:11554448; http://dx.doi.org/10.1089/15230860152542961
73. Bihlmaier K, Mesecke N, Kloeppel C, Herrmann JM. The disulfide relay of the intermembrane space of mitochondria: an oxygen-sensing system? Ann N Y Acad Sci 2008; 1147:293-302; PMID:19076451; http://dx.doi.org/10.1196/annals.1427.005
74. Schägger H, Pfeiffer K. Supercomplexes in the respiratory chains of yeast and mammalian mitochondria. EMBO J 2000; 19:1777-83; PMID:10775262; http://dx.doi.org/10.1093/emboj/19.8.1777
75. Lenaz G, Baracca A, Barbero G, Bergamini C, Dalmonte ME, Del Sole M, Faccioli M, Falasca A, Fato R, Genova ML, et al. Mitochondrial respiratory chain super-complex I-III in physiology and pathology. Biochim Biophys Acta 2010; 1797:633-40; PMID:20116362; http://dx.doi.org/10.1016/j.bbabio.2010.01.025
76. Wittig I, Schägger H. Supramolecular organization of ATP synthase and respiratory chain in mitochondrial membranes. Biochim Biophys Acta 2009; 1787:672-80; PMID:19168025; http://dx.doi.org/10.1016/j.bbabio.2008.12.016
77. Martindale JL, Holbrook NJ. Cellular response to oxidative stress: signaling for suicide and survival. J Cell Physiol 2002; 192:1-15; PMID:12115731; http://dx.doi.org/10.1002/jcp.10119
78. Macedo GS, Lisbôa da Motta L, Giacomazzi J, Netto CB, Manfredini V, Vanzin CS, Vargas CR, Hainaut P, Klamt F, Ashton-Prolla P. Increased oxidative damage in carriers of the germline TP53 p.R337H mutation. PLoS One 2012; 7:e47010; PMID:23056559; http://dx.doi.org/10.1371/journal.pone.0047010
79. Li T, Kon N, Jiang L, Tan M, Ludwig T, Zhao Y, Baer R, Gu W. Tumor suppression in the absence of p53-mediated cell-cycle arrest, apoptosis, and senescence. Cell 2012; 149:1269-83; PMID:22682249; http://dx.doi.org/10.1016/j. cell.2012.04.026
80. Magrané J, Hervias I, Henning MS, Damiano M, Kawamata H, Manfredi G. Mutant SOD1 in neuronal mitochondria causes toxicity and mitochondrial dynamics abnormalities. Hum Mol Genet 2009; 18:4552-64; PMID:19779023; http://dx.doi.org/10.1093/hmg/ddp421
81. Bunz F, Dutriaux A, Lengauer C, Waldman T, Zhou S, Brown JP, Sedivy JM, Kinzler KW, Vogelstein B. Requirement for p53 and p21 to sustain G2 arrest after DNA damage. Science 1998; 282:1497-501; PMID:9822382; http://dx.doi.org/10. 1126/science.282.5393.1497
82. Ferecatu I, Le Floch N, Bergeaud M, Rodríguez-Enfedaque A, Rincheval V, Oliver L, Vallette FM, Mignotte B, Vayssière JL. Evidence for a mitochondrial localization of the retinoblastoma protein. BMC Cell Biol 2009; 10:50; PMID:19555499; http://dx.doi.org/10.1186/1471-2121-10-50
83. Lemaire C, Hamel P, Velours J, Dujardin G. Absence of the mitochondrial AAA protease Yme1p restores F0-ATPase subunit accumulation in an oxa1 deletion mutant of Saccharomyces cerevisiae. J Biol Chem 2000; 275:23471-5; PMID:10816574; http://dx.doi.org/10.1074/jbc.M002045200