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Open Access 01-12-2015 | Review

Mitophagy and cancer

Authors: Aparajita H Chourasia, Michelle L Boland, Kay F Macleod

Published in: Cancer & Metabolism | Issue 1/2015

Abstract

Mitophagy is a selective form of macro-autophagy in which mitochondria are selectively targeted for degradation in autophagolysosomes. Mitophagy can have the beneficial effect of eliminating old and/or damaged mitochondria, thus maintaining the integrity of the mitochondrial pool. However, mitophagy is not only limited to the turnover of dysfunctional mitochondria but also promotes reduction of overall mitochondrial mass in response to certain stresses, such as hypoxia and nutrient starvation. This prevents generation of reactive oxygen species and conserves valuable nutrients (such as oxygen) from being consumed inefficiently, thereby promoting cellular survival under conditions of energetic stress. The failure to properly modulate mitochondrial turnover in response to oncogenic stresses has been implicated both positively and negatively in tumorigenesis, while the potential of targeting mitophagy specifically as opposed to autophagy in general as a therapeutic strategy remains to be explored. The challenges and opportunities that come with our heightened understanding of the role of mitophagy in cancer are reviewed here.

Mizushima N, Komatsu M. Autophagy: renovation of cells and tissues. Cell. 2011;147:728–41.PubMed

Mizushima N, Yoshimori T, Ohsumi Y. The role of Atg proteins in autophagosome formation. Ann Rev Cell Dev Biol. 2011;27:107–32.

Levine B, Kroemer G. Autophagy in the pathogenesis of disease. Cell. 2008;132:27–42.PubMedCentralPubMed

Glick D, Barth S, Macleod KF. Autophagy: cellular & molecular mechanisms. J Pathol. 2010;221:3–12.PubMedCentralPubMed

Kroemer G, Marino G, Levine B. Autophagy and the integrated stress response. Mol Cell. 2010;40:280–93.PubMedCentralPubMed

Rabinowitz JD, White E. Autophagy and metabolism. Science. 2010;330:1344–8.PubMedCentralPubMed

Mizushima N, Klionsky DJ. Protein turnover via autophagy: implications for metabolism. Ann Rev Nutr. 2007;27:19–40.

Kim I, Rodriguez-Enriquez S, Lemasters JJ. Selective degradation of mitochondria by mitophagy. Arch Biochem Biophys. 2007;462:245–53.PubMedCentralPubMed

Komatsu M, Kurokawa H, Waguri S, Taguchi K, Kobayashi A, Ichimura Y, et al. The selective autophagy substrate p62 activates the stress responsive transcription factor Nrf2 through inactivation of Keap1. Nat Cell Biol. 2010;12:213–23.PubMed

10.

Johansen T, Lamark T. Selective autophagy mediated by autophagic adaptor proteins. Autophagy. 2011;7:1–18.

11.

Weidberg H, Shvets E, Elazar Z. Biogenesis and cargo selectivity of autophagosomes. Ann Rev Biochem. 2011;80:125–56.PubMed

12.

Rogov V, Dotsch V, Johansen T, Kirkin V. Interactions between autophagy receptors and ubiquitin-like proteins form the molecular basis for selective autophagy. Mol Cell. 2014;53:167–78.PubMed

13.

Green DR, Levine B. To be or not to be? How selective autophagy and cell death govern cell fate. Cell. 2014;157:65–75.PubMed

14.

Tolkovsky AM. Mitophagy. Biochim Biophy Acta. 2009;1793:1508–15.

15.

Youle RJ, Narendra DP. Mechanisms of mitophagy. Nat Rev Mol Biol. 2011;12:9–14.

16.

Boland ML, Chourasia AH, Macleod KF. Mitochondrial dysfunction in cancer. Frontiers in Oncology. 2013;3:292–320.PubMedCentralPubMed

17.

Twig G, Elorza A, Molina AJ, Mohamed H, Wikstrom JD, Walzer G, et al. Fission and selective fusion govern mitochondrial segregation and elimination by autophagy. EMBO J. 2008;27:433–46.PubMedCentralPubMed

18.

Rambold AS, Kostelecky B, Elia N, Lippincott-Schwartz J. Tubular network formation protects mitochondrial from autophagosomal degradation during nutrient starvation. Proc Natl Acad Sci U S A. 2011;108:10190–5.PubMedCentralPubMed

19.

Gomes LC, Di Benedetto G, Scorrano L. During autophagy mitochondria elongate, are spared from degradation and sustain cell viability. Nat Cell Biol. 2011;13:589–98.PubMedCentralPubMed

20.

Matsuda N, Sato S, Shiba K, Okatsu K, Saisho K, Gautier SA, et al. PINK1 stabilized by mitochondrial depolarization recruits Parkin to damaged mitochondria and activates latent Parkin for mitophagy. J Cell Biol. 2010;189:211–21.PubMedCentralPubMed

21.

Narendra DP, Jin SM, Tanaka AJ, Suen DF, Gautier CA, Shen J, et al. PINK1 is selectively stabilized on impaired mitochondria to activate Parkin. PLoS Biol. 2010;8:e1000298.PubMedCentralPubMed

22.

Vives-Bauza C, Zhou C, Huang Y, Cui M, de Vries RL, Kim J, et al. PINK1-dependent recruitment of Parkin to mitochondria in mitophagy. Proc Natl Acad Sci U S A. 2010;107:378–83.PubMedCentralPubMed

23.

Head B, Griparic L, Amiri M, Gandre-Babbe S, van der Bliek AM. Inducible proteolytic inactivation of OPA1 mediated by the OMA1 protease in mammalian cells. J Cell Biol. 2009;187:959–66.PubMedCentralPubMed

24.

Ehses S, Raschke I, Mancuso G, Bernacchia A, Geimer S, Tondera D, et al. Regulation of OPA1 processing and mitochondrial fusion by m-AAA protease isoenzymes and OMA1. J Cell Biol. 2009;187:1023–36.PubMedCentralPubMed

25.

Schriner SE, Linford NJ, Martin GM, Treuting P, Ogburn CE, Emond M, et al. Extension of murine life span by overexpression of catalase targeted to mitochondria. Science. 2005;308:1909–11.PubMed

26.

Lee HY, Choi CS, Birkenfeld AL, Alves TC, Jornayvaz FR, Jurczak MJ, et al. Targeted expression of catalase to mitochondria prevents age-associated reductions in mitochondrial function and insulin resistance. Cell Metab. 2010;12:668–74.PubMedCentralPubMed

27.

Zhang H, Gao P, Fukuda R, Kumar G, Krishnamachary B, Zeller KI, et al. HIF-1 inhibits mitochondrial biogenesis and cellular respiration in VHL-deficient renal cell carcinoma by repression of c-Myc activity. Cancer Cell. 2007;11:407–20.PubMed

28.

Tracy K, Dibling BC, Spike BT, Knabb JR, Schumacker P, Macleod KF. BNIP3 is a RB/E2F target gene required for hypoxia-induced autophagy. Mol Cell Biol. 2007;27:6229–42.PubMedCentralPubMed

29.

Tracy K, Macleod KF. Regulation of mitochondrial integrity, autophagy and cell survival by BNIP3. Autophagy. 2007;3:616–9.PubMedCentralPubMed

30.

Narendra D, Youle RJ. Targeting mitochondrial dysfunction: role for PINK1 and Parkin in mitochondrial quality control. Antioxid Redox Signal. 2011;14:1929–38.PubMedCentralPubMed

31.

Zhang J, Ney PA. Role of BNIP3 and NIX in cell death, autophagy and mitophagy. Cell Death Diff. 2009;16:939–46.

32.

Hollville E, Carroll RG, Cullen SP, Martin SG. Bcl-2 family proteins participate in mitochondrial quality control by regulating Parkin/PINK1-dependent mitophagy. Mol Cell. 2014;55:451–66.

33.

Cesari R, Martin ES, Calin GA, Pentimalli F, Bichi R, McAdams H, et al. Parkin, a gene implicated in autosomal recessive juvenile parkinsonism, is a candidate tumor suppressor gene on chromosome 6q25-q27. Proc Natl Acad Sci U S A. 2003;100:5956–61.PubMedCentralPubMed

34.

Gong Y, Zack TI, Morris LGT, Lin K, Hukkelhoven E, Raheja R, et al. Pan-cancer genetic analysis identifies PARK2 as a master regulator of G1/S cyclins. Nat Gen. 2014;46:588–94.

35.

Fujiwara M, Marusawa H, Wang HQ, Iwai A, Ikeuchi K, Imai Y, et al. Parkin as a tumor suppressor gene for hepatocellular carcinoma. Oncogene. 2008;27:6002–11.PubMed

36.

Kim KY, Stevens MV, Akter MH, Rusk SE, Huang RJ, Cohen A, et al. Parkin is a lipid-responsive regulator of fat uptake in mice and mutant human cells. J Clin Invest. 2011;121:3701–12.PubMedCentralPubMed

37.

Zhang C, Lin M, Wu R, Wang X, Yang BG, Levine AJ, et al. Parkin, a p53 target gene, mediates the role of p53 in glucose metabolism and the Warburg effect. Proc Natl Acad Sci U S A. 2011;108:16259–64.PubMedCentralPubMed

38.

Narendra D, Walker JE, Youle R. Mitochondrial quality control mediated by PINK1 and Parkin: links to parkinsonism. Cold Spring Harb Perspect Biol. 2012;4:a011338.PubMedCentralPubMed

39.

Kane LA, Lazarou M, Fogel AI, Li Y, Yamano K, Sarraf SA, et al. PINK1 phosphorylates ubiquitin to activate Parkin E3 ubiquitin ligase activity. J Cell Biol. 2014;205:143–53.PubMedCentralPubMed

40.

Ordureau A, Sarraf SA, Duda DM, Heo JM, Jedrychowski MP, Sviderskiy VO, et al. Quantitative proteomics reveal a feedforward mechanisms for mitochondrial PARKIN translocation and ubiquitin chain synthesis. Mol Cell. 2014;56:360–75.PubMed

41.

Wang X, Winter D, Ashrafi G, Schlehe J, Wong YL, Selkoe D, et al. PINK1 and Parkin target Miro for phosphorylation and degradation to arrest mitochondrial motility. Cell. 2011;147:893–906.PubMedCentralPubMed

42.

Chan NC, Salazar AM, Pham AH, Sweredoski MJ, Kolawa NJ, Graham RL, et al. Broad activation of the ubiquitin-proteasome system by Parkin is critical for mitophagy. Hum Mol Genet. 2011;20:1726–37.PubMedCentralPubMed

43.

Sarraf SA, Raman M, Guarani-Pereira V, Sowa ME, Huttlin EL, Gygi SP, et al. Landscape of the PARKIN-dependent ubiquitylome in response to mitochondrial depolarization. Nature. 2013;496:372–6.PubMedCentralPubMed

44.

Chen Y, Dorn GW. PINK1-phosphorylated Mitofusin-2 is a Parkin receptor for culling damaged mitochondria. Science. 2013;340:471–5.PubMedCentralPubMed

45.

Bingol B, Tea JS, Phu L, Reichelt M, Bakalarski CE, Song Q, et al. The mitochondrial deubiquitinase USP30 opposes parkin-mediated mitophagy. Nature. 2014;510:370–5.PubMed

46.

Lee JY, Nagano Y, Taylor JP, Lim KL, Yao TP. Disease-causing mutations in parkin impair mitochondrial ubiquitination, aggregation, and HDAC6-dependent mitophagy. J Cell Biol. 2010;189:671–9.PubMedCentralPubMed

47.

Geisler S, Holmström KM, Skujat D, Fiesel FC, Rothfuss OC, Kahle PJ, et al. PINK1/Parkin-mediated mitophagy is dependent on VDAC1 and p62/SQSTM1. Nat Cell Biol. 2010;12:119–31.PubMed

48.

Novak I. Mitophagy: a complex mechanism of mitochondrial removal. Antioxid Redox Signal. 2012;17:794–802.PubMed

49.

Narendra D, Kane LA, Hauser DN, Fearnley IM, Youle RJ. p62/SQSTM1 is required for Parkin-induced mitochondrial clustering but not mitophagy; VDAC1 is dispensable for both. Autophagy. 2010;6:1090–106.PubMedCentralPubMed

50.

Houtkooper RH, Mouchiroud L, Ryu D, Moullan N, Katsyuba E, Knott G, et al. Mitonuclear protein imbalance as a conserved longevity mechanism. Nature. 2013;497:451–7.PubMed

51.

Lee JY, Koga H, Kawaguchi Y, Tang W, Wong E, Gao YS, et al. HDAC6 controls autophagosome maturation essential for ubiquitin-selective quality-control autophagy. The EMBO J. 2010;29:969–80.

52.

Shin JH, Ko HS, Kang HS, Lee YK, Lee YI, Pletinkova O, et al. PARIS (ZNF746) repression of PGC-1α contributes to neurodegeneration in Parkinson's disease. Cell. 2011;144:689–702.PubMedCentralPubMed

53.

Chinnadurai G, Vijayalingam S, Gibson SB. BNIP3 subfamily BH3-only proteins: mitochondrial stress sensors in normal and pathological functions. Oncogene. 2009;27:S114–27.

54.

Bruick RK. Expression of the gene encoding the proapoptotic Nip3 protein is induced by hypoxia. Proc Natl Acad Sci U S A. 2000;97:9082–7.PubMedCentralPubMed

55.

Guo K, Searfoss G, Krolikowski D, Pagnoni M, Franks C, Clark K, et al. Hypoxia induces the expression of the pro-apoptotic gene BNIP3. Cell Death Diff. 2001;8:367–76.

56.

Kasper LH, Boussouar F, Boyd K, Xu W, Biesen M, Rehg J, et al. Two transcriptional mechanisms cooperate for the bulk of HIF-1-responsive gene expression. EMBO J. 2005;24:3846–58.PubMedCentralPubMed

57.

Dayan F, Roux D, Brahimi-Horn C, Pouyssegur J, Mazure NM. The oxygen sensing factor-inhibiting hypoxia-inducible factor-1 controls expression of distinct genes through the bi-functional transcriptional character of hypoxia-inducible factor-1a. Cancer Res. 2006;66:3688–98.PubMed

58.

Pouyssegur J, Dayan F, Mazure NM. Hypoxia signalling in cancer and approaches to enforce tumour regression. Nature. 2006;441:437–43.PubMed

59.

Shaw J, Yurkova N, Zhang T, Gang H, Aguilar F, Weidman D, et al. Antagonism of E2F-1 regulated Bnip3 transcription by NF-kappaB is essential for basal cell survival. Proc Natl Acad Sci U S A. 2008;105:20734–9.PubMedCentralPubMed

60.

Mammucari C, Milan G, Romanello V, Masiero E, Rudolf R, Del Piccolo P, et al. FoxO3 controls autophagy in skeletal muscle in vivo. Cell Metab. 2007;6:458–71.PubMed

61.

Kalas W, Swiderek E, Rapak A, Kopij M, Rak JW, Strzadala L. H-ras up-regulates expression of BNIP3. Anticancer Res. 2011;31:2869–75.PubMed

62.

Wu SY, Lan SH, Cheng DE, Chen WK, Shen CH, Lee YR, et al. Ras-related tumorigenesis is suppressed by BNIP3-mediated autophagy through inhibition of cell proliferation. Neoplasia. 2011;13:1171–82.PubMedCentralPubMed

63.

Feng X, Liu X, Zhang W, Xiao W. p53 directly suppresses BNIP3 expression to protect against hypoxia-induced cell death. EMBO J. 2011;30:3397–415.PubMedCentralPubMed

64.

Fei P, Wang W, Kim SH, Wang S, Burns TF, Sax JK, et al. Bnip3L is induced by p53 under hypoxia, and its knockdown promotes tumor growth. Cancer Cell. 2005;6:597–609.

65.

Diwan A, Koesters AG, Odley AM, Pushkaran S, Baines CP, Spike BT, et al. Unrestrained erythroblast development in Nix−/− mice reveals a mechanism for apoptotic modulation of erythropoiesis. Proc Natl Acad Sci U S A. 2007;104:6794–9.PubMedCentralPubMed

66.

Glick D, Zhang W, Beaton M, Marsboom G, Gruber M, Simon MC, et al. BNip3 regulates mitochondrial function and lipid metabolism in the liver. Mol Cell Biol. 2012;32:2570–84.PubMedCentralPubMed

67.

Schweers RL, Zhang J, Randall MS, Loyd MR, Li W, Dorsey FC, et al. NIX is required for programmed mitochondrial clearance during reticulocyte maturation. Proc Natl Acad Sci U S A. 2007;104:19500–5.PubMedCentralPubMed

68.

Sandoval H, Thiagarajan P, Dasgupta SK, Scumacker A, Prchal JT, Chen M, et al. Essential role for Nix in autophagic maturation of red cells. Nature. 2008;454:232–5.PubMedCentralPubMed

69.

Vande Velde C, Cizeau J, Dubik D, Alimonti J, Brown T, Israels S, et al. BNIP3 and genetic control of necrosis-like cell death through the mitochondrial permeability transition pore. Mol Cell Biol. 2000;20:5454–68.PubMedCentralPubMed

70.

Sulistijo ES, Jaszewksi TM, MacKenzie KR. Sequence-specific dimerization of the transmembrane domain of the "BH3-only" protein BNIP3 in membranes and detergent. J Biol Chem. 2003;278:51950–6.PubMed

71.

Sulistijo ES, MacKenzie KR. Structural basis for dimerization of the BNIP3 transmembrane domain. Biochem. 2009;48:5106–20.

72.

Schwarten M, Mohrluder J, Ma P, Stoldt M, Thielman Y, Stangler T, et al. Nix binds to GABARAP: a possible crosstalk between apoptosis and autophagy. Autophagy. 2009;5:690–8.PubMed

73.

Hanna RA, Quinsay MN, Orogo AM, Giang K, Rikka S, Gustafsson AB. Microtubule-associated protein 1 light chain 3 (LC3) interacts with BNip3 protein to selectively remove endoplasmic reticulum and mitochondria via autophagy. J Biol Chem. 2012;287:19094–104.PubMedCentralPubMed

74.

Melser S, Chatelain EH, Lavie J, Mahfouf W, Jose C, Obre E, et al. Rheb regulates mitophagy induced by mitochondrial energetic status. Cell Metab. 2013;17:719–30.PubMed

75.

Kanki T, Wang KKW, Caio Y, Baba M, Klionsky DJ. Atg32 is a mitochondrial protein that confers selectivity during mitophagy. Dev Cell. 2009;17:98–109.PubMedCentralPubMed

76.

Okamoto K, Kondo-Okamoto N, Ohsumi Y. Mitochondrial-anchored receptor Atg32 mediates degradation of mitochondria via selective autophagy. Dev Cell. 2009;17:87–97.PubMed

77.

Zhu Y, Massen S, Terenzio M, Lang V, Chen-Lindner S, Eils R, et al. Modulation of serines 17 and 24 in the LC3-interacting region of BNIP3 determines pro-survival mitophagy VS. apoptosis. J Biol Chem. 2012;288:1099–113.PubMedCentralPubMed

78.

Ray R, Chen G, Vande Velde C, Cizeau J, Park JH, Reed JC, et al. BNIP3 heterodimerizes with Bcl-2/Bcl-XL and induces cell death independent of a Bcl-2 homology 3 (BH3) domain at both mitochondrial and nonmitochondrial sites. J Biol Chem. 2000;275:1439–48.PubMed

79.

Hardwick JM, Youle RJ. Snapshot: Bcl2 proteins. Cell. 2009;23:404.

80.

Graham RM, Frazier DP, Thompson JW, Haliko S, Li H, Wasserlauf BJ, et al. A unique pathway of cardiac myocyte death caused by hypoxia-acidosis. J Exp Biol. 2004;207:3189–200.PubMed

81.

Al-Mehdi AB, Pastukh VM, Swiger BM, Reed DJ, Patel MR, Bardwell GC, et al. Perinuclear mitochondrial clustering creates an oxidant-rich nuclear domain required for hypoxia-induced transcription. Sci Signal. 2012;5:ra47.PubMedCentralPubMed

82.

Landes T, Emorine LJ, Courilleau D, Rojo M, Belenguer P, Arnaune-Pelloquin L. The BH3-only BNip3 binds to the dynamin Opa1 to promote mitochondrial fragmentation and apoptosis by distinct mechanisms. EMBO Rep. 2010;11:459–65.PubMedCentralPubMed

83.

Quinsay MN, Lee YS, Rikka S, Sayen MR, Molkentin JD, Gottlieb RA, et al. BNip3 mediates permeabilization of mitochondria and relase of cytochrome c via a novel mechanism. J Mol Cell Cardiol. 2009;481:146–56.

84.

Lee YK, Lee HY, Hanna RA, Gustafsson AB. Mitochondrial autophagy by Bnip3 involves Drp1-mediated mitochondrial fission and recruitment of Parkin in cardiac myocytes. Am J Physiol Heart Circ Physiol. 2011;301:H1924–31.PubMedCentralPubMed

85.

Li Y, Wang Y, Kim E, Beemiller P, Wang CY, Swanson J, et al. Bnip3 mediates the hypoxia-induced inhibition on mTOR by interacting with Rheb. J Biol Chem. 2007;282:35803–13.PubMed

86.

Sowter HM, Ferguson M, Pym C, Watson P, Fox SB, Han C, et al. Expression of the cell death genes BNip3 and Nix in ductal carcinoma in situ of the breast; correlation of BNip3 levels with necrosis and grade. J Path. 2003;201:573–80.PubMed

87.

Sowter HM, Ratcliffe PJ, Watson P, Greenberg AH, Harris AL. HIF1-dependent regulation of hypoxic induction of the cell death factors BNIP3 and NIX in human tumors. Cancer Res. 2001;61:6669–73.PubMed

88.

Koop EA, van Laar T, D.F. vW, Weger RA, van der Wall E, van Diest PJ. Expression of BNIP3 in invasive breast cancer: correlations with the hypoxic response and clinicopathological features. BMC Cancer. 2009;9:175–82.PubMedCentralPubMed

89.

Okami J, Simeone DM, Logsdon CD. Silencing of the hypoxia-inducible cell death protein BNIP3 in pancreatic cancer. Cancer Res. 2004;64:5338–46.PubMed

90.

Murai M, Toyota M, Satoh A, Suzuki H, Akino K, Mita H, et al. Aberrant methylation associated with silencing BNIP3 expression in haematopoietic tumours. Br J Cancer. 2005;92:1165–72.PubMedCentralPubMed

91.

Murai M, Toyota M, Suzuki H, Satoh A, Sasaki Y, Akino K, et al. Aberrant methylation and silencing of the BNIP3 gene in colorectal and gastric cancer. Clin Cancer Res. 2005;11:1021–7.PubMed

92.

Calvisi DF, Ladu S, Gorden A, Farina M, Lee JS, Conner E, et al. Mechanistic and prognostic significance of aberrant methylation in the molecular pathogenesis of human hepatocellular carcinoma. J Clin Invest. 2007;117:2713–22.PubMedCentralPubMed

93.

Erkan M, Kleef J, Esposito I, Giese T, Ketterer K, Buchler MW, et al. Loss of BNIP3 expression is a late event in pancreatic cancer contributing to chemoresistance and worsened prognosis. Oncogene. 2005;24:4421–32.PubMed

94.

Akada M, Crnogorac-Jurcevic T, Lattimore S, Mahon P, Lopes R, Sunamura M, et al. Intrinsic chemoresistance to gemcitabine is associated with decreased expression of BNIP3 in pancreatic cancer. Clin Cancer Res. 2005;11:3094–101.PubMed

95.

van Diest PJ, Suijkerbuijk KPM, Koop EA, Weger RA, van der Wall E. Low levels of BNIP3 promoter hypermethylation in invasive breast cancer. Anal Cell Pathol. 2010;33:175–6.

96.

Beroukhim R, Mermel CH, Porter D, Wei G, Raychaudhuri S, Donovan J, et al. The landscape of somatic copy-number alteration across human cancers. Nature. 2010;463:899–905.PubMedCentralPubMed

97.

Burton TR, Henson ES, Baijal P, Elsenstat DD, Gibson SB. The pro-cell death Bcl-2 family member, BNIP3, is localized to the nucleus of human glial cells: implications for glioblastoma multiforme tumor cell survival under hypoxia. Int J Cancer. 2006;118:1660–9.PubMedCentralPubMed

98.

Tan EY, Campo L, Han C, Turley H, Pezzella F, Gatter KC, et al. BNIP3 as a progression marker in primary human breast cancer; opposing functions in in situ versus invasive cancer. Clin Cancer Res. 2007;13:467–74.PubMed

99.

Shaida N, Launchbury R, Boddy JL, Jones C, Campo L, Turley H, et al. Expression of BNIP3 correlates with hypoxia-inducible factor (HIF)-1alpha, HIF-2alpha and the androgen receptor in prostate cancer and is regulated directly by hypoxia but not androgens in cell lines. Prostate. 2008;68:336–43.PubMed

100.

Manka D, Spicer Z, Millhorn DE. Bcl-2/adenovirus E1B 19 kDa interacting protein-3 knockdown enables growth of breast cancer metastases in the lung, liver and bone. Cancer Res. 2005;65:11689–93.PubMed

101.

Ding WX, Ni HM, Li M, Liao Y, Chen X, Stolz DB, et al. Nix is critical to two distinct phases of mitophagy, reactive oxygen species-mediated autophagy induction and Parkin-ubiquitin-p62-mediated mitochondrial priming. J Biol Chem. 2010;285:27879–90.PubMedCentralPubMed

102.

Diwan A, Krenz M, Syed FM, Wansapura J, Ren X, Koesters AG, et al. Inhibition of ischemic cardiomyocyte apoptosis through targeted ablation of BNip3 restrains postinfarction remodeling in mice. J Clin Invest. 2007;117:2825–33.PubMedCentralPubMed

103.

Lokireddy S, Wijesoma IW, Teng SC, Bonala S, Gluckman PD, McFarlane C, et al. The ubiquitin ligase Mul1 induces mitophagy in skeletal muscle in response to muscle-wasting stimuli. Cell Metab. 2012;16:613–24.PubMed

104.

Liu L, Feng D, Chen G, Chen M, Zheng Q, Song P, et al. Mitochondrial outer-membrane protein FUNDC1 mediates hypoxia-induced mitophagy in mammalian cells. Nat Cell Biol. 2012;14:177–85.PubMed

105.

Wu WK, Tian W, Hu Z, Chen G, Huang L, Li W, et al. ULK1 translocates to mitochondria and phosphorylates FUNDC1 to regulate mitophagy. EMBO Rep. 2014;15:566–75.PubMed

106.

Li W, Zhang X, Zhuang H, Chen HG, Chen Y, Tian W, et al. MicroRNA-137 is a novel hypoxia-responsive microRNA that inhibits mitophagy via regulation of two mitophagy receptors FUNDC1 and NIX. J Biol Chem. 2014;289:10691–701.PubMed

107.

Guo JY, Chen HY, Mathew R, Fan J, Strohecker AM, Karsli-Uzumbas G, et al. Activated Ras requires autophagy to maintain oxidative metabolism and tumorigenesis. Genes Dev. 2011;25:460–70.PubMedCentralPubMed

108.

Guo JY, Karsli-Uzunbas G, Mathew R, Aisner SC, Kamphorst JJ, Strohecker AM, et al. Autophagy suppresses progression of K-ras-induced lung tumors to oncocytomas and maintains lipid homeostasis. Genes Dev. 2013;27:1447–61.PubMedCentralPubMed

109.

Rosenfeldt MT, O'Prey J, Morton JP, Nixon C, MacKay G, Mrowinska A, et al. p53 status determines the role of autophagy in pancreatic tumour development. Nature. 2013;504:296–300.PubMed

110.

Strohecker AM, Guo JY, Karsli-Uzunbas G, Price SM, Chen GJ, Mathew R, et al. Autophagy sustains mitochondrial glutamine metabolism and growth of BrafV600E-driven lung tumors. Cancer Discov. 2013;3:1272–85.PubMed

111.

Rao S, Tortola L, Perlot T, Wirnsberger G, Novatchkova M, Nitsch R, et al. A dual role for autophagy in a murine model of lung cancer. Nat Comm. 2014;5:3056–70.

112.

Gasparre G, Romeo G, Rugolo M, Porcelli AM. Learning from oncocytic tumors: why choose inefficient mitochondria? Biochim Biophy Acta. 1807;2011:633–42.

113.

Settembre C, Di Malta C, Polito VA, Garcia Arencibia M, Vetrini F, Erdin S, et al. TFEB links autophagy to lysosomal biogenesis. Science. 2011;332:1429–33.PubMedCentralPubMed

114.

Maes H, Rubio N, Garg AD, Agostinis P. Autophagy: shaping the tumor microenvironment and therapeutic response. Trends Mol Med. 2013;19:428–46.PubMed

115.

Michaud M, Martins I, Sukkurwala AQ, Adjemian S, Ma Y, Pellegatti P, et al. Autophagy-dependent anticancer immune responses induced by chemotherapeutic agents in mice. Science. 2011;334:1573–7.PubMed

116.

Wei H, Wei S, Gan B, Peng X, Zou W, Guan JL. Suppression of autophagy by FIP200 deletion inhibits mammary tumorigenesis. Genes Dev. 2011;25:1510–27.PubMedCentralPubMed

117.

Lock R, Kenific CM, Leidal AM, Salas E, Debnath J. Autophagy dependent production of secreted factors facilitates oncogenic RAS-driven invasion. Cancer Discov. 2014;4:466–79.PubMedCentralPubMed

118.

Sena LA, Chandel NS. Physiological roles of mitochondrial reactive oxygen species. Mol Cell. 2012;48:158–67.PubMedCentralPubMed

119.

Shackelford DB, Abt E, Gerken L, Vasquez DS, Seki A, Leblanc M, et al. LKB1 inactivation dictates therapeutic response of non-small cell lung cancer to the metabolism drug phenformin. Cancer Cell. 2013;23:143–58.PubMedCentralPubMed

120.

Birsoy K, Possemato R, Lorbeer FK, Bayraktar EC, Thiru P, Yucel B, et al. Metabolic determinants of cancer cell sensitivity to glucose limitation and biguanides. Nature. 2014;508:108–12.PubMedCentralPubMed

121.

Zhang X, Fryknas M, Hernlund E, Fayad W, De Milito A, Olofsson MH, et al. Induction of mitochondrial dysfunction as a strategy for targeting tumour cells in metabolically compromised microenvironments. Nat Comm. 2014;5:3295–309.

122.

Viale A, Pettazzoni P, Lyssiotis CA, Ying H, Sánchez N, Marchesini M, et al. Oncogene ablation-resistant pancreatic cancer cells depend on mitochondrial function. Nature. 2014;514:628–32.PubMed

123.

Durieux J, Wolff S, Dillin A. The cell-non-autonomous nature of electron transport chain-mediated longevity. Cell. 2011;144:79–91.PubMedCentralPubMed

124.

Liang XH, Jackson S, Seaman M, Brown K, Kempkes B, Hibshoosh H, et al. Induction of autophagy and inhibition of tumorigenesis by beclin1. Nature. 1999;402:672–6.PubMed

125.

Qu X, Yu JJ, Bhagat G, Furuya N, Hibshoosh H, Troxel A, et al. Promotion of tumorigenesis by heterozygous disruption of the beclin 1 autophagy gene. J Clin Invest. 2003;112:1809–20.PubMedCentralPubMed

126.

Degenhardt K, Mathew R, Beaudoin B, Bray K, Anderson KL, Chen G, et al. Autophagy promotes tumor cell survival and restricts necrosis, inflammation and tumorigenesis. Cancer Cell. 2006;10:51–64.PubMedCentralPubMed

127.

Laddha SV, Ganesan S, Chan CS, White E. Mutational landscape of the essential autophagy gene BECN1 in human cancers. Mol Cancer Res. 2014;12:485–90.PubMed

128.

Li L, Shen C, Nakamura E, Ando K, Signoretti S, Beroukhim R, et al. SQSTM1 is a pathogenic target of 5q copy number gains in kidney cancer. Cancer Cell. 2013;24:738–50.PubMedCentralPubMed

129.

Thompson HG, Harris JW, Wold BJ, Lin FT, Brody JP. p62 overexpression in breast tumors and regulation by prostate-derived Ets factor in breast cancer. Oncogene. 2003;22:2322–33.PubMed

130.

Duran A, Linares JF, Galvez AS, Wikenheiser K, Flores JM, Diaz-Meco MT, et al. The signaling adaptor p62 is an important NF-kB mediator in tumorigenesis. Cancer Cell. 2008;13:343–54.PubMed

131.

Kuo WL, Sharifi MN, Lingen MW, Karrison T, Nagilla M, Ahmed O, et al. Macro-autophagy deficiency promotes resistance of squamous cell carcinomas of the head and neck to phosphatidylinositol 3-kinase and AKT inhibitors. PLoS One. 2014;9:e90171.PubMedCentralPubMed

132.

Chano T, Kontani K, Teramoto K, Okabe H, Ikegawa S. Truncating mutations of RB1CC1 in human breast cancer. Nat Gen. 2002;31:285–8.

Title: Mitophagy and cancer
Authors: Aparajita H Chourasia
Michelle L Boland
Kay F Macleod
Publication date: 01-12-2015
Publisher: BioMed Central
Published in: Cancer & Metabolism / Issue 1/2015
Electronic ISSN: 2049-3002
DOI: https://doi.org/10.1186/s40170-015-0130-8

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