Regulation and function of mitophagy in development and cancer

Autophagy

Volumn 9, Issue 11, 2013, Pages 1720-1736

  Lu, Haiqi ^a   Li, Guangliang ^b   Liu, Leiming ^a   Feng, Lifeng ^a   Wang, Xian ^a   Jin, Hongchuan ^a  

^a ZHEJIANG UNIVERSITY   (China)

^b ZHEJIANG UNIVERSITY   (China)

Author keywords

Autophagy; Cancer; Development; Energy metabolism; Mitochondria; Mitophagy; Tumor microenvironment; Tumorigenesis; Warburg effect

Indexed keywords

4 [4 (4' CHLORO 2 BIPHENYLYLMETHYL) 1 PIPERAZINYL] N [4 [3 DIMETHYLAMINO 1 (PHENYLTHIOMETHYL)PROPYLAMINO] 3 NITROBENZENESULFONYL]BENZAMIDE; BECLIN 1; BRCA1 PROTEIN; CELL CYCLE PROTEIN 37; ENDOPHILIN; HEAT SHOCK PROTEIN 90; MITOGEN ACTIVATED PROTEIN KINASE; PHOSPHATIDYLINOSITOL 3 KINASE; PROTEIN KINASE B;

ADIPOGENESIS; ADIPOSE TISSUE; APOPTOSIS; ARTICLE; AUTOPHAGOSOME; AUTOPHAGY; B CELL LYMPHOMA; BREAST CANCER; CANCER INHIBITION; CARBON SOURCE; CARCINOGENESIS; CELL DIFFERENTIATION; CELL MATURATION; CELL PROLIFERATION; CELL SURVIVAL; CHROMOSOMAL INSTABILITY; CLINICAL TRIAL (TOPIC); DEVELOPMENT; EMBRYO DEVELOPMENT; ENDOPLASMIC RETICULUM; ENERGY YIELD; ERYTHROBLAST; ERYTHROCYTE; FIBROBLAST; GENE EXPRESSION; GLUCOSE METABOLISM; GLYCOLYSIS; HUMAN; HYPOXIA; LIVER CELL CARCINOMA; LOSS OF FUNCTION MUTATION; LYMPHOCYTE DIFFERENTIATION; MACROAUTOPHAGY; MEMBRANE DEPOLARIZATION; METASTASIS; MITOCHONDRIAL MEMBRANE; MITOCHONDRIAL MEMBRANE POTENTIAL; MITOPHAGY; NONHUMAN; OVARY CANCER; OXIDATIVE PHOSPHORYLATION UNCOUPLING; PEXOPHAGY; PROTEIN DEPLETION; PROTEIN PHOSPHORYLATION; RADIOSENSITIVITY; SACCHAROMYCES CEREVISIAE; T LYMPHOCYTE; TISSUE DIFFERENTIATION; TUMOR GROWTH; TUMOR MICROENVIRONMENT; UBIQUITINATION;

MAMMALIA;

AUTOPHAGY; CANCER; DEVELOPMENT; ENERGY METABOLISM; MITOCHONDRIA; MITOPHAGY; TUMOR MICROENVIRONMENT; TUMORIGENESIS; WARBURG EFFECT;

ANIMALS; GROWTH AND DEVELOPMENT; HUMANS; MITOCHONDRIAL DEGRADATION; MODELS, BIOLOGICAL; NEOPLASMS; SACCHAROMYCES CEREVISIAE;

EID: 84887495000     PISSN: 15548627     EISSN: 15548635     Source Type: Journal    
DOI: 10.4161/auto.26550     Document Type: Article

References (184)

1. Klionsky DJ. Autophagy: from phenomenology to molecular understanding in less than a decade. Nat Rev Mol Cell Biol 2007; 8: 931-7; PMID: 17712358; http://dx.doi.org/10.1038/nrm2245 (Pubitemid 47622558)
2. Xie Z, Klionsky DJ. Autophagosome formation: core machinery and adaptations. Nat Cell Biol 2007; 9: 1102-9; PMID: 17909521; http://dx.doi.org/ 10.1038/ncb1007-1102 (Pubitemid 47500484)
3. Youle RJ, Narendra DP. Mechanisms of mitophagy. Nat Rev Mol Cell Biol 2 011; 12: 9-14; PMID: 21179058; http://dx.doi.org/10.1038/nrm3028
4. Ding WX, Yin XM. Mitophagy: mechanisms, pathophysiological roles, and analysis. Biol Chem 2012; 393: 547-64; PMID: 22944659; http://dx.doi.org/10. 1515/h s z -2012 - 0119
5. Monastyrska I, Reggiori F, Klionsky DJ. Harpooning the Cvt complex to the phagophore assembly site. Autophagy 2008; 4: 914-6; PMID: 18708760
6. Oku M, Sakai Y. Pexophagy in Pichia pastoris. Methods Enzymol 2008; 451: 217-28; PMID: 19185723; http://dx.doi.org/10.1016/S 0 076 - 6879 ( 0 8 ) 03215-1
7. MacIntosh GC, Bassham DC. The connection between ribophagy, autophagy and ribosomal RNA decay. Autophagy 2 011; 7: 662-3; PMID: 21460615; http://dx.doi.org/10.4161/auto.7.6.15447
8. Kudchodkar SB, Levine B. Viruses and autophagy. Rev Med Virol 2009; 19: 359-78; PMID: 19750559; http://dx.doi.org/10.1002/rmv.630
9. Lemasters JJ. Selective mitochondrial autophagy, or mitophagy, as a targeted defense against oxidative stress, mitochondrial dysfunction, and aging. Rejuvenation Res 2005; 8: 3-5; PMID: 15 7 9 8 3 67; http://dx.doi.org/10.1089/ rej.2005.8.3
10. Clark SL Jr. Cellular differentiation in the kidneys of newborn mice studies with the electron microscope. J Biophys Biochem Cytol 1957; 3: 349-62; PMID: 13438920; http://dx.doi.org/10.1083/jcb.3.3.349
11. Kim I, Rodriguez-Enriquez S, Lemasters JJ. Selective degradation of mitochondria by mitophagy. Arch Biochem Biophys 2007; 462: 245-53; PMID: 174752 0 4; http://dx.doi.org/10.1016/j. abb.2007.03.034 (Pubitemid 46876640)
12. Johri A, Beal MF. Mitochondrial dysfunction in neurodegenerative diseases. J Pharmacol Exp Ther 2012; 342: 619-30; PMID: 22700435; http://dx.doi.org/10.1124/jpet.112.192138
13. Cotán D, Cordero MD, Garrido-Maraver J, Oropesa-Ávila M, Rodríguez-Hernández A, Gómez Izquierdo L, De la Mata M, De Miguel M, Lorite JB, Infante ER, et al. Secondary coenzyme Q10 deficiency triggers mitochondria degradation by mitophagy in MELAS fibroblasts. FASEB J 2011; 25: 2669-87; PMID: 21551 2 3 8; http://dx.doi.org/10.1096/fj.10-165340
14. Yen WL, Klionsky DJ. How to live long and prosper: autophagy, mitochondria, and aging. Physiology (Bethesda) 2008; 23: 248-62; PMID: 18927201; http://dx.doi.org/10.1152/physiol.00013.2008
15. Zungu M, Schisler J, Willis MS. All the little pieces. -Regulation of mitochondrial fusion and fission by ubiquitin and small ubiquitin-like modifer and their potential relevance in the heart.-. Circ J 2011; 75: 2513-21; PMID: 22001293; http://dx.doi.org/10.1253/circj.CJ-11-0967
16. Zhou R, Yazdi AS, Menu P, Tschopp J. A role for mitochondria in NLRP3 inflammasome activation. Nature 2 0 11; 469: 221-5; PMID: 2 1 1 2 4 3 15; http://dx.doi.org/10.1038/nature09663
17. Kanki T, Wa ng K, Cao Y, Baba M, Klionsky DJ. Atg32 is a mitochondrial protein that confers selectivity during mitophagy. Dev Cell 2009; 17: 98-109; PMID: 19619 495; http://dx.doi.org/10.1016/j. devcel.2009.06.014
18. Nakatogawa H, Suzuki K, Kamada Y, Ohsumi Y. Dynamics and diversity in autophagy mechanisms: lessons from yeast. Nat Rev Mol Cell Biol 2009; 10: 458-67; PMID: 19491929; http://dx.doi.org/10.1038/nrm2708
19. Okamoto K, Kondo-Okamoto N, Ohsumi Y. Mitochondria-anchored receptor Atg32 mediates degradation of mitochondria via selective autophagy. Dev Cell 2009; 17: 87-97; PMID: 19619494; http://dx.doi.org/10.1016/j.devcel.2009.06.013
20. Aoki Y, Kanki T, Hirota Y, Kurihara Y, Saigusa T, Uchiumi T, Kang D. Phosphorylation of Serine 114 on Atg32 mediates mitophagy. Mol Biol Cell 2011; 22: 3206-17; PMID: 21757540; http://dx.doi.org/10.1091/mbc.E11-02-0145
21. Mao K, Wang K, Zhao M, Xu T, Klionsky DJ. Two MAPK-signaling pathways are required for mitophagy in Saccharomyces cerevisiae. J Cell Biol 2 011; 19 3: 755-67; PMID: 215 7 6 3 9 6; http://dx.doi.org/10.1083/jcb.201102092
22. Mao K, Klionsky DJ. MAPKs regulate mitophagy in Saccharomyces cerevisiae. Autophagy 2011; 7: 156 4-5; PMID: 22024747; http://dx.doi.org/10.4161/auto.7. 12.17971
23. Kanki T, Wang K, Baba M, Bartholomew CR, Lynch-Day MA, Du Z, Geng J, Mao K, Yang Z, Yen WL, et al. A genomic screen for yeast mutants defective in selective mitochondria autophagy. Mol Biol Cell 2009; 20: 4730-8; PMID: 19 7939 21; http://dx.doi.org/10.1091/mbc.E09-03-0225
24. Joo JH, Dorsey FC, Joshi A, Hennessy-Walters KM, Rose KL, McCastlain K, Zhang J, Iyengar R, Jung CH, Suen DF, et a l. Hsp90-Cdc37 chaperone complex regulates Ulk1- and Atg13-mediated mitophagy. Mol Cell 2011; 43: 572-85; PMID: 21855797; http://dx.doi.org/10.1016/j.molcel.2011.06.018
25. Watanabe Y, Kobayashi T, Yamamoto H, Hoshida H, Akada R, Inagaki F, Ohsumi Y, Noda NN. Structure-based analyses reveal distinct binding sites for Atg2 and phosphoinositides in Atg18. J Biol Chem 2012; 287: 31681-90; PMID: 2 2 851171; http://dx.doi.org/10.1074/jbc.M112.397570
26. Kaiser SE, Mao K, Taherbhoy AM, Yu S, Olszewski JL, Duda DM, Kurinov I, Deng A, Fenn TD, Klionsky DJ, et al. Noncanonical E2 recruitment by the autophagy E1 revealed by Atg7-Atg3 and Atg7-Atg10 structures. Nat Struct Mol Biol 2012; 19: 1242-9; PMID: 23142976; http://dx.doi.org/10.1038/nsmb. 2415
27. Yu ZQ, Ni T, Hong B, Wang HY, Jiang FJ, Zou S, Chen Y, Zheng XL, Klionsky DJ, Liang Y, et al. Dual roles of Atg8-PE deconjugation by Atg4 in autophagy. Autophagy 2012; 8: 883-92; PMID: 22652539; http://dx.doi.org/10.4161/auto.19652
28. Walczak M, Martens S. Dissecting the role of the Atg12-Atg5-Atg16 complex during autophagosome formation. Autophagy 2013; 9: 424-5; PMID: 23321721; http://dx.doi.org/10.4161/a uto.2 2931
29. Itakura E, Mizushima N. Atg14 and UVRAG: mutually exclusive subunits of mammalian Beclin 1-PI3K complexes. Autophagy 2009; 5: 534-6; PMID: 19223761; http://dx.doi.org/10.4161/auto.5.4.8062
30. Zhang J, Randall MS, Loyd MR, Dorsey FC, Kundu M, Cleveland JL, Ney PA. Mitochondrial clearance is regulated by Atg7-dependent and -independent mechanisms during reticulocyte maturation. Blood 2009; 114: 157-64; PMID: 19417210
31. Mortensen M, Ferguson DJ, Edelmann M, Kessler B, Morten KJ, Komatsu M, Simon AK. Loss of autophagy in erythroid cells leads to defective removal of mitochondria and severe anemia in vivo. Proc Natl Acad Sci U S A 2010; 107: 832-7; PMID: 20080761; http://dx.doi.org/10.1073/pnas.0913170107
32. Yen WL, Legakis JE, Nair U, Klionsky DJ. Atg27 is required for autophagy-dependent cycling of Atg9. Mol Biol Cell 2007; 18: 581-93; PMID: 17135291; http://dx.doi.org/10.1091/mbc.E06-07-0612 (Pubitemid 46213226)
33. Tang F, Watkins JW, Bermudez M, Gray R, Gaban A, Portie K, Grace S, Kleve M, Craciun G. A life-span extending form of autophagy employs the vacuole-vacuole fusion machinery. Autophagy 2008; 4: 874-86; PMID: 18690010
34. Ragusa MJ, Stanley RE, Hurley JH. Architecture of the Atg17 complex as a scaffold for autophagosome biogenesis. Cell 2012; 15 1: 15 0 1-12; PMID: 2 3 2 19 4 8 5; http://dx.doi.org/10.1016/j.cell.2012.11.028
35. Mendl N, Occhipinti A, Müller M, Wild P, Dikic I, Reichert AS. Mitophagy in yeast is independent of mitochondrial fission and requires the stress response gene WHI2. J Cell Sci 2011; 124: 1339-50; PMID: 21429936; http://dx.doi.org/10.1242/jcs.076406
36. Legakis JE, Yen WL, Klionsky DJ. A cycling protein complex required for selective autophagy. Autophagy 2007; 3: 422-32; PMID: 17426 4 40 (Pubitemid 47293723)
37. Nice DC, Sato TK, Stromhaug PE, Emr SD, Klionsky DJ. Cooperative binding of the cytoplasm to vacuole targeting pathway proteins, Cvt13 and Cvt20, to phosphatidylinositol 3-phosphate at the pre-autophagosomal structure is required for selective autophagy. J Biol Chem 2002; 277: 30198-207; PMID: 12048214; http://dx.doi.org/10.1074/jbc. M204736200
38. Austriaco NR Jr. Review: to bud until death: the genetics of ageing in the yeast, Saccharomyces. Yeast 1996; 12: 623-30; PMID: 8810036; http://dx.doi.org/10.1002/(SICI)1097-0061(19960615)12: 73.0.CO;2-G (Pubitemid 26201764)
39. Kissová I, Deffieu M, Manon S, Camougrand N. Uth1p is involved in the autophagic degradation of mitochondria. J Biol Chem 2004; 279: 39068-74; PMID: 15247238; http://dx.doi.org/10.1074/jbc. M406960200 (Pubitemid 39296069)
40. Kissová I, Salin B, Schaeffer J, Bhatia S, Manon S, Camougrand N. Selective and non-selective autophagic degradation of mitochondria in yeast. Autophagy 2007; 3: 329-36; PMID: 17377488 (Pubitemid 46986337)
41. Ta l R, Winter G, Ecker N, Klionsky DJ, Abeliovich H. Aup1p, a yeast mitochondrial protein phosphatase homolog, is required for efficient stationary phase mitophagy and cell survival. J Biol Chem 2007; 282: 5617-24; PMID: 17166847; http://dx.doi.org/10.1074/jbc.M605940200 (Pubitemid 47093789)
42. Ruan H, Yan Z, Sun H, Jiang L. The YCR079w gene confers a rapamycin-resistant function and encodes the sixth type 2C protein phosphatase in Saccharomyces cerevisiae. FEMS Yeast Res 2007; 7: 209-15; PMID: 170 02782; http://dx.doi. or g/10.1111/j.15 67-13 6 4. 2 0 0 6. 0 016 0. x
43. Gasser T. Molecular pathogenesis of Parkinson disease: insights from genetic studies. Expert Rev Mol Med 2009; 11:e22; PMID: 1963100 6; http://dx.doi.org/10.1017/S1462399409001148
44. Clark IE, Dodson MW, Jiang C, Cao JH, Huh JR, Seol JH, Yoo SJ, Hay BA, Guo M. Drosophila pink1 is required for mitochondrial function and interacts genetically with parkin. Nature 2006; 441: 1162-6; PMID: 16672981; http://dx.doi.org/10.1038/nature04779 (Pubitemid 43990738)
45. Poole AC, Thomas RE, Andrews LA, McBride HM, Whitworth AJ, Pallanck LJ. The PINK1/Parkin pathway regulates mitochondrial morphology. Proc Natl Acad Sci U S A 2008; 105: 1638-43; PMID: 18230723; http://dx.doi.org/10.1073/pnas. 0709336105 (Pubitemid 351346567)
46. Narendra D, Tanaka A, Suen DF, Youle RJ. Parkin is recruited selectively to impaired mitochondria and promotes their autophagy. J Cell Biol 2008; 183: 795-803; PMID: 19029340; http://dx.doi.org/10.1083/jcb.200809125
47. Suen DF, Narendra DP, Tanaka A, Manfredi G, Youle RJ. Parkin overexpression selects against a deleterious mtDNA mutation in heteroplasmic cybrid cells. Proc Natl Acad Sci U S A 2010; 107: 11835-40; PMID: 20547844; http://dx.doi.org/10.1073/pnas.0914569107
48. Yang Y, Ouyang Y, Yang L, Beal MF, McQuibban A, Vogel H, Lu B. Pink1 regulates mitochondrial dynamics through interaction with the fission/f usion mac hiner y. Proc Natl Acad Sci U S A 2008; 105: 7070-5; PMID: 18443288; http://dx.doi.org/10.1073/pnas.0711845105 (Pubitemid 351754531)
49. Poulogiannis G, McIntyre RE, Dimitriadi M, Apps JR, Wilson CH, Ichimura K, Luo F, Cantley LC, Wyllie AH, Adams DJ, et al. PARK2 deletions occur frequently in sporadic colorectal cancer and accelerate adenoma development in Apc mutant mice. Proc Natl Acad Sci U S A 2010; 107: 15145-50; PMID: 20696900; http://dx.doi.org/10.1073/pnas.1009941107
50. Vives-Bauza C, Zhou C, Huang Y, Cui M, d e Vr i e s RL, Kim J, May J, Tocilescu MA, Liu W, Ko HS, et al. PINK1-dependent recruitment of Parkin to mitochondria in mitophagy. Proc Natl Acad Sci U S A 2010; 107: 378-83; PMID: 19966284; http://dx.doi.org/10.1073/pnas.0911187107
51. Zhou C, Huang Y, Shao Y, May J, Prou D, Perier C, Dauer W, Schon EA, Przedborski S. The kinase domain of mitochondrial PINK1 faces the cytoplasm. Proc Natl Acad Sci U S A 2008; 105: 12022-7; PMID: 18687899; http://dx.doi.org/10.1073/pnas.0802814105
52. Narendra DP, Jin SM, Tanaka A, Suen DF, Gautier CA, Shen J, Cookson MR, Youle RJ. PINK1 is selectively stabilized on impaired mitochondria to activate Parkin. PLoS Biol 2010; 8:e1000298; PMID: 20126261; http://dx.doi.org/10.1371/ journal. pbio.1000298
53. Greene AW, Grenier K, Aguileta MA, Muise S, Farazifard R, Haque ME, McBride HM, Park DS, Fon EA. Mitochondrial processing peptidase regulates PINK1 processing, import and Parkin recruitment. EMBO Rep 2012; 13: 378-85; PMID: 22354088; http://dx.doi.org/10.1038/embor.2012.14
54. Meissner C, Lorenz H, Weihofen A, Selkoe DJ, Lemberg MK. The mitochondrial intramembrane protease PARL cleaves human Pink1 to regulate Pink1 trafficking. J Neurochem 2011; 117: 856-67; PMID: 21426348; http://dx.doi. o r g/10.1111/j.147 1-4159. 2 011.0 7 253. x
55. Lazarou M, Jin SM, Kane LA, Youle RJ. Role of PINK1 binding to the TOM complex and alternate intracellular membranes in recruitment and activation of the E3 ligase Parkin. Dev Cell 2012; 22: 320-33; PMID: 22280891; http://dx.doi.org/10.1016/j. devcel.2011.12.014
56. Lutz AK, Exner N, Fett ME, Schlehe JS, Kloos K, Lämmermann K, Brunner B, Kurz-Drexler A, Vogel F, Reichert AS, et al. Loss of parkin or PINK1 function increases Drp1-dependent mitochondrial fragmentation. J Biol Chem 2009; 284: 22938-51; PMID: 195 4 6216; http://dx.doi.org/10.1074/jbc. M109.035774
57. Dagda RK, Cherra SJ 3rd, Kulich SM, Ta ndon A, Park D, Chu CT. Loss of PINK1 function promotes mitophagy through effects on oxidative stress and mitochondrial fission. J Biol Chem 2009; 284: 13843-55; PMID: 19 2 7 9 012; http://dx.doi.org/10.1074/jbc. M808515200
58. Kirkin V, McEwan DG, Novak I, Dikic I. A role for ubiquitin in selective autophagy. Mol Cell 2009; 34: 259-69; PMID: 19450525; http://dx.doi.org/10.1016/ j.molcel.2009.04.026
59. Gegg ME, Cooper JM, Chau KY, Rojo M, Schapira AH, Taanman J W. Mitofusin 1 and mitofusin 2 are ubiquitinated in a PINK1/parkin-dependent manner upon induction of mitophagy. Hum Mol Genet 2010; 19: 4861-70; PMID: 20871098; http://dx.doi.org/10.1093/hmg/ddq419
60. Pankiv S, Clausen TH, Lamark T, Brech A, Bruun JA, Outzen H, Øvervatn A, Bjørkøy G, Johansen T. p62/SQSTM1 binds directly to Atg8/LC3 to facilitate degradation of ubiquitinated protein aggregates by autophagy. J Biol Chem 2007; 282: 24131-45; PMID: 17580304; http://dx.doi.org/10.1074/jbc. M702824200 (Pubitemid 47328003)
61. Okatsu K, Saisho K, Shimanuki M, Nakada K, Shitara H, Sou YS, Kimura M, Sato S, Hattori N, Komatsu M, et al. p62/SQSTM1 cooperates with Parkin for perinuclear clustering of depolarized mitochondria. Genes Cells 2010; 15: 887-900; PMID: 20604804
62. 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; PMID: 20890124; http://dx.doi.org/10.4161/auto.6.8.13426
63. 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; PMID: 20457763; http://dx.doi.org/10. 1083/jcb.201001039
64. Lee JY, Koga H, Kawaguchi Y, Tang W, Wong E, Gao YS, Pandey UB, Kaushik S, Tre sse E, Lu J, et al. HDAC6 controls autophagosome maturation essential for ubiquitin-selective quality-control autophagy. EMBO J 2010; 29: 969-80; PMID: 20075865; http://dx.doi.org/10.1038/emboj.2009.405
65. Tanaka A, Cleland MM, Xu S, Narendra DP, Suen DF, Karbowski M, Youle RJ. Proteasome and p97 mediate mitophagy and degradation of mitofusins induced by Parkin. J Cell Biol 2010; 191: 1367-80; PMID: 21173115; http://dx.doi.org/10. 1083/jcb.201007013
66. Geisler S, Holmström KM, Skujat D, Fiesel FC, Rothfuss OC, Kahle PJ, Springer W. PINK1/Parkin-mediated mitophagy is dependent on VDAC1 and p62/SQSTM1. Nat Cell Biol 2010; 12: 119-31; PMID: 20098416; http://dx.doi.org/ 10.1038/ncb2012
67. Kim Y, Park J, Kim S, Song S, Kwon SK, Lee SH, Kitada T, Kim JM, Chung J. PINK1 controls mitochondrial localization of Parkin through direct phosphorylation. Biochem Biophys Res Commun 2008; 377: 975-80; PMID: 18957282; http://dx.doi.org/10.1016/j.bbrc.2008.10.104
68. Shiba-Fukushima K, Imai Y, Yoshida S, Ishihama Y, Kanao T, Sato S, Hattori N. PINK1-mediated phosphorylation of the Parkin ubiquitin-like domain primes mitochondrial translocation of Parkin and regulates mitophagy. Sci Rep 2012; 2: 1002; PMID: 23256036; http://dx.doi.org/10.1038/srep01002
69. Feng D, Liu L, Zhu Y, Chen Q. Molecular signaling toward mitophagy and its physiological significance. Exp Cell Res 2013; 319: 1697-705; PMID: 23603281; http://dx.doi.org/10.1016/j.yexcr.2013.03.034
70. Ding WX, Ni HM, Li M, Liao Y, Chen X, Stolz DB, Dorn GW 2nd, Yin XM. 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; PMID: 20573959; http://dx.doi.org/10.1074/jbc.M110.119537
71. Liu L, Feng D, Chen G, Chen M, Zheng Q, Song P, Ma Q, Zhu C, Wang R, Qi W, et al. Mitochondrial outer-membrane protein FUNDC1 mediates hypoxia-induced mitophagy in mammalian cells. Nat Cell Biol 2012; 14: 177-85; PMID: 22267086; http://dx.doi.org/10.1038/ncb2422
72. Grüllich C, Duvoisin RM, Wiedmann M, van Leyen K. Inhibition of 15-lipoxygenase leads to delayed organelle degradation in the reticulocyte. FEBS Lett 2001; 489: 51-4; PMID: 11231012; http://dx.doi.org/10.1016/S0014-5793(01) 02080-4 (Pubitemid 32176004)
73. Fimia GM, Corazzari M, Antonioli M, Piacentini M. Ambra1 at the crossroad between autophagy and cell deat h. Onc o gene 2 01 3; 32: 3 3 1 1-8; PMID: 23069654; http://dx.doi.org/10.1038/onc.2012.455.
74. Levin DE. Cell wall integrity signaling in Saccharomyces cerevisiae. Microbiol Mol Biol Rev 2005; 69: 262-91; PMID: 15944456; http://dx.doi.org/10. 1128/MMBR.69.2.262-291.2005 (Pubitemid 40847940)
75. 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; PMID: 22505714; http://dx.doi.org/10.1074/jbc.M111.322933
76. Ishihara M, Urushido M, Hamada K, Matsumoto T, Shimamura Y, Ogata K, Inoue K, Ta n ig uc h i Y, Horino T, Fujieda M, et al. Sestrin-2 and BNIP3 regulate autophagy and mitophagy in renal tubular cells in acute kidney injury. Am J Physiol Renal Physiol 2013; 305:F495-509; PMID: 23698117; http://dx.doi.org/10.1152/ajprenal.00642.2012.
77. Zhang J, Ney PA. NIX induces mitochondrial autophagy in reticulocytes. Autophagy 2008; 4: 354-6; PMID: 18623629 (Pubitemid 351458098)
78. Schweers RL, Zhang J, Randall MS, Loyd MR, Li W, Dorsey FC, Kundu M, Opferman JT, Cleveland JL, Miller JL, et al. NIX is required for programmed mitochondrial clearance during reticulocyte maturation. Proc Natl Acad Sci U S A 2007; 104: 1950 0-5; PMID: 18048346; http://dx.doi.org/10.1073/pnas.0708818104
79. Sandoval H, Thiagarajan P, Dasgupta SK, Schumacher A, Prchal JT, Chen M, Wang J. Essential role for Nix in autophagic maturation of erythroid cells. Nature 2008; 454: 232-5; PMID: 18454133; http://dx.doi.org/10.1038/nature07006 (Pubitemid 351969889)
80. Novak I, Kirkin V, McEwan DG, Zhang J, Wild P, Rozenknop A, Rogov V, Löhr F, Popovic D, Occhipinti A, et al. Nix is a selective autophagy receptor for mitochondrial clearance. EMBO Rep 2010; 11: 45-51; PMID: 20010802; http://dx.doi.org/10.1038/embor.2009.256
81. Kanki T. Nix, a receptor protein for mitophagy in mammals. Autophagy 2010; 6: 433-5; PMID: 20200478; http://dx.doi.org/10.4161/auto.6.3.11420
82. Sentelle RD, Senkal CE, Jiang W, Ponnusamy S, Gencer S, Selvam SP, Ramshesh VK, Peterson YK, Lemasters JJ, Szulc ZM, et al. Ceramide targets autophagosomes to mitochondria and induces lethal mitophagy. Nat Chem Biol 2012; 8: 831-8; PMID: 22922758; http://dx.doi.org/10.1038/nchembio.1059
83. Ta ng D, Kang R, Livesey KM, Kroemer G, Billiar TR, Van Houten B, Zeh HJ 3rd, Lotze MT. High-mobility group box 1 is essential for mitochondrial quality control. Cell Metab 2011; 13: 701-11; PMID: 216 4 1551; http://dx.doi.org/10. 1016/j. cmet.2011.04.008
84. Westfa ll PJ, Ballon DR, Thorner J. When the stress of your environment makes you go HOG wild. Science 2004; 306: 1511-2; PMID: 155 678 51; http://dx.doi.org/10.1126/scienc e.110 4879 (Pubitemid 39564938)
85. Itoh H, Komatsuda A, Ohtani H, Wakui H, Imai H, Sawada K, Otaka M, Ogura M, Suzuki A, Hamada F. Mammalian HSP60 is quickly sorted into the mitochondria under conditions of dehydration. Eur J Biochem 2002; 269: 5931-8; PMID: 12444982; http://dx.doi.org/10.1046/j.1432-1033.2002.03317.x (Pubitemid 35425590)
86. Park SJ, Shin JH, Kim ES, Jo YK, Kim JH, Hwang JJ, Kim JC, Cho DH. Mitochondrial fragmentation caused by phenanthroline promotes mitophagy. FEBS Lett 2012; 586: 4303-10; PMID: 23123158; http://dx.doi.org/10.1016/j.febslet. 2012.10.035
87. Silvestri L, Caputo V, Bellacchio E, Atorino L, Dallapiccola B, Valente EM, Casari G. Mitochondrial import and enzymatic activity of PINK1 mutants associated to recessive parkinsonism. Hum Mol Genet 2005; 14: 3477-92; PMID: 16207731; http://dx.doi.org/10.1093/hmg/ddi377 (Pubitemid 41672130)
88. Ankel-Simons F, Cummins JM. Misconceptions about mitochondria and mammalian fertilization: implications for theories on human evolution. Proc Natl Acad Sci U S A 1996; 93: 13859-63; PMID: 8943026; http://dx.doi.org/10.1073/ pnas.93.24.13859 (Pubitemid 26424211)
89. Sato M, Sato K. Degradation of paternal mitochondria by fertilization-triggered autophagy in C elegans embryos. Science 2011; 334: 1141-4; PMID: 219 9 8 252; http://dx.doi.org/10.1126/science.1210333
90. Al Rawi S, Louvet-Vallée S, Djeddi A, Sachse M, Culetto E, Hajjar C, Boyd L, Legouis R, Galy V. Postfertilization autophagy of sperm organelles prevents paternal mitochondrial DNA transmission. Science 2011; 334: 1144-7; PMID: 22033522; http://dx.doi.org/10.1126/science.1211878
91. Zhou Q, Li H, Xue D. Elimination of paternal mitochondria through the lysosomal degradation pathway in C elegans. Cell Res 2011; 21: 1662-9; PMID: 22105480; http://dx.doi.org/10.1038/c r. 2 011.182
92. Sutovsky P. Ubiquitin-dependent proteolysis in mammalian spermatogenesis, fertilization, and sperm quality control: killing three birds with one stone. Microsc Res Tech 20 03; 6 1: 88-10 2; PMID: 12672125; http://dx.doi.org/10.1002/ jemt.10319 (Pubitemid 36469238)
93. Sutovsky P, Moreno RD, Ramalho-Santos J, Dominko T, Simerly C, Schatten G. Ubiquitin tag for sperm mitochondria. Nature 1999; 402: 371-2; PMID: 10586873; http://dx.doi.org/10.1038/46466 (Pubitemid 129544815)
94. Thompson WE, Ramalho-Santos J, Sutovsky P. Ubiquitination of prohibitin in mammalian sperm mitochondria: possible roles in the regulation of mitochondrial inheritance and sperm quality control. Biol Reprod 2003; 69: 254-60; PMID: 12646488; http://dx.doi.org/10.1095/biolreprod.102.010975 (Pubitemid 36806830)
95. Sutovsky P, Moreno RD, Ramalho-Santos J, Dominko T, Simerly C, Schatten G. Ubiquitinated sperm mitochondria, selective proteolysis, and the regulation of mitochondrial inheritance in mammalian embryos. Biol Reprod 2000; 63: 582-90; PMID: 10906068; http://dx.doi.org/10.1095/biolreprod63.2.582 (Pubitemid 30639950)
96. Mortensen M, Ferguson DJP, Edelmann M, Kessler B, Morten KJ, Komatsu M, Simon AK. Loss of autophagy in erythroid cells leads to defective removal of mitochondria and severe anemia in vivo. Proc Natl Acad Sci U S A 2010; 107: 832-7; PMID: 20080761; http://dx.doi.org/10.1073/pnas.0913170107
97. Kundu M, Lindsten T, Yang CY, Wu J, Zhao F, Zhang J, Selak MA, Ney PA, Thompson CB. Ulk1 plays a critical role in the autophagic clearance of mitochondria and ribosomes during reticulocyte maturation. Blood 2008; 112: 1493-502; PMID: 18539900; http://dx.doi.org/10.1182/blood-2008-02-137398
98. Barde I, Rauwel B, Marin-Florez RM, Corsinotti A, Laurenti E, Verp S, Offner S, Marquis J, Kapopoulou A, Vanic ek J, et al. A KRAB/KAP1-miRNA cascade regulates erythropoiesis through stage-specific control of mitophagy. Science 2013; 340: 350-3; PMID: 23493425; http://dx.doi.org/10.1126/science.1232398
99. Singh R, Xiang Y, Wang Y, Baikati K, Cuervo AM, Luu YK, Ta ng Y, Pessin JE, Schwartz GJ, Czaja MJ. Autophagy regulates adipose mass and differentiation in mice. J Clin Invest 2009; 119: 3329-39; PMID: 19855132
100. Baerga R, Zhang Y, Chen PH, Goldman S, Jin S. Targeted deletion of autophagy-related 5 (atg5) impairs adipogenesis in a cellular model and in mice. Autophagy 2009; 5: 1118-30; PMID: 19 8 4 415 9; http://dx.doi.org/10.4161/auto. 5.8.9991
101. Zhang Y, Goldman S, Baerga R, Zhao Y, Komatsu M, Jin S. Adipose-specific deletion of autophagy-related gene 7 (atg7) in mice reveals a role in adipogenesis. Proc Natl Acad Sci U S A 2009; 106: 19860-5; PMID: 19910529
102. Pua HH, Dzhagalov I, Chuck M, Mizushima N, He Y W. A critical role for the autophagy gene Atg5 in T cell survival and proliferation. J Exp Med 2007; 204: 25-31; PMID: 17190837; http://dx.doi.org/10.1084/jem.20061303 (Pubitemid 46148752)
103. Pua HH, Guo J, Komatsu M, He YW. Autophagy is essential for mitochondrial clearance in mature T lymphocytes. J Immunol 2009; 182: 4046-55; PMID: 19299702; http://dx.doi.org/10.4049/jimmunol.0801143
104. Pua HH, He Y W. Mitophag y in the little lymphocytes: an essential role for autophagy in mitochondrial clearance in T lymphocytes. Autophagy 2009; 5: 745-6; PMID: 19398889; http://dx.doi.org/10.4161/auto.5.5.8702
105. Xilouri M, Stefanis L. Autophagic pathways in Parkinson disease and related disorders. Expert Rev Mol Med 2011; 13:e8; PMID: 21418705; http://dx.doi.org/10.1017/S1462399411001803
106. Chaturvedi RK, Beal MF. Mitochondria targeted therapeutic approaches in Parkinson's and Huntington's diseases. Mol Cell Neurosci 2013; 55: 101-14; PMID: 23220289; http://dx.doi.org/10.1016/j.mcn.2012.11.011
107. Moreira PI, Siedlak SL, Wa ng X, Santos MS, Oliveira CR, Tabaton M, Nunomura A, Szweda LI, Aliev G, Smith MA, et al. Increased autophagic degradation of mitochondria in Alzheimer disease. Autophagy 2007; 3: 614-5; PMID: 17786024 (Pubitemid 350060061)
108. Costa V, Scorrano L. Shaping the role of mitochondria in the pathogenesis of Huntington's disease. EMBO J 2012; 31: 1853-64; PMID: 22446390; http://dx.doi.org/10.1038/emboj.2012.65
109. Mathew R, White E. Autophagy in tumorigenesis and energy metabolism: friend by day, foe by night. Curr Opin Genet Dev 2011; 21: 113-9; PMID: 21255998; http://dx.doi.org/10.1016/j.gde.2010.12.008
110. Gredilla R, Garm C, Stevnsner T. Nuclear and mitochondrial DNA repair in selected eukaryotic aging model systems. Oxid Med Cell Longev 2012; 2012: 282438.
111. Azad MB, Chen Y, Gibson SB. Regulation of autophagy by reactive oxygen species (ROS): implications for cancer progression and treatment. Antioxid Redox Signal 2009; 11: 777-90; PMID: 18828708; http://dx.doi.org/10.1089/ars.2008. 2270
112. Lisanti MP, Martinez-Outschoorn UE, Chiavarina B, Pavlides S, Whitaker-Menezes D, Tsirigos A, Witkiewicz A, Lin Z, Balliet R, Howell A, et al. Understanding the "lethal" drivers of tumor-stroma co-evolution: emerging role(s) for hypoxia, oxidative stress and autophagy/mitophagy in the tumor micro-environment. Cancer Biol Ther 2010; 10: 537-42; PMID: 20861671; http://dx.doi.org/10.4161/cbt.10.6.13370
113. Wang X, Jin H. The epigenetic basis of the Warburg effect. Epigenetics 2010; 5: 566-8; PMID: 20622527; http://dx.doi.org/10.4161/epi.5.7.12662
114. Warburg O. On the origin of cancer cells. Science 1956; 123: 309-14; PMID: 13298683; http://dx.doi.org/10.1126/science.123.3191.309
115. Warburg O. On respiratory impairment in cancer cells. Science 1956; 124: 269-70; PMID: 13351639
116. Martinez-Outschoorn UE, Sotgia F, Lisanti MP. Power surge: supporting cells "fuel" cancer cell mitochondria. Cell Metab 2012; 15: 4-5; PMID: 22225869; http://dx.doi.org/10.1016/j. c m e t. 2 011.1 2. 011
117. Martinez-Outschoorn UE, Pestell RG, Howell A, Ty k o c i n s k i ML, Nagajyothi F, Machado FS, Ta now it z HB, Sotgia F, Lisanti MP. Energy transfer in "parasitic" cancer metabolism: mitochondria are the powerhouse and Achilles' heel of tumor cells. Cell Cycle 2011; 10: 4208-16; PMID: 22033146; http://dx.doi.org/10.4161/cc.10.24.18487
118. Pavlides S, Vera I, Gandara R, Sneddon S, Pestell RG, Mercier I, Martinez-Outschoorn UE, Whitaker-Menezes D, Howell A, Sotgia F, et al. Warburg meets autophagy: cancer-associated fibroblasts accelerate tumor growth and metastasis via oxidative stress, mitophagy, and aerobic glycolysis. Antioxid Redox Signal 2012; 16: 1264-84; PMID: 21883043; http://dx.doi.org/10.1089/ars. 2011.4243
119. Pavlides S, Whitaker-Menezes D, Castello-Cros R, Flomenberg N, Witkiewicz AK, Frank PG, Casimiro MC, Wang C, Fortina P, Addya S, et al. The reverse Warburg effect: aerobic glycolysis in cancer associated fibroblasts and the tumor stroma. Cell Cycle 2009; 8: 3984-4001; PMID: 19923890; http://dx.doi.org/10.4161/cc.8.23.10238
120. Witkiewicz AK, Dasgupta A, Sotgia F, Mercier I, Pestell RG, Sabel M, Kleer CG, Brody JR, Lisanti MP. An absence of stromal caveolin-1 expression predicts early tumor recurrence and poor clinical outcome in human breast cancers. Am J Pathol 2009; 174: 2023-34; PMID: 194114 48; http://dx.doi.org/10. 2353/ajpath.2009.080873
121. Sloan EK, Ciocca DR, Pouliot N, Natoli A, Restall C, Henderson MA, Fanelli MA, Cuello-Carrión FD, Gago FE, Anderson RL. Stromal cell expression of caveolin-1 predicts outcome in breast cancer. Am J Pathol 2009; 174: 2035-43; PMID: 194114 49; http://dx.doi.org/10.2353/ajpath.2009.080924
122. Sotgia F, Martinez-Outschoorn UE, Howell A, Pestell RG, Pavlides S, Lisanti MP. Caveolin-1 and cancer metabolism in the tumor microenvironment: markers, models, and mechanisms. Annu Rev Pathol 2012; 7: 423-67; PMID: 22077552; http://dx.doi.org/10.114 6/a n nu rev-pat hol- 011811-120856
123. Sotgia F, Martinez-Outschoorn UE, Pavlides S, Howell A, Pestell RG, Lisanti MP. Understanding the Warburg effect and the prognostic value of stromal caveolin-1 as a marker of a lethal tumor microenvironment. Breast Cancer Res 2 011; 13: 213; PMID: 21867571; http://dx.doi.org/10.1186/bcr2892
124. Pavlides S, Tsirigos A, Migneco G, Whitaker-Menezes D, Chiavarina B, Flomenberg N, Frank PG, Casimiro MC, Wang C, Pestell RG, et al. The autophagic tumor stroma model of cancer: Role of oxidative stress and ketone production in fueling tumor cell metabolism. Cell Cycle 2010; 9: 3485-505; PMID: 20861672; http://dx.doi.org/10.4161/cc.9.17.12721
125. Razani B, Zhang XL, Bitzer M, von Gersdorff G, Böttinger EP, Lisanti MP. Caveolin-1 regulates transforming growth factor (TGF)-beta/SMAD signaling through an interaction with the TGF-beta type I receptor. J Biol Chem 2001; 276: 6727-38; PMID: 111024 4 6; http://dx.doi.org/10.1074/jbc. M008340200
126. Guido C, Whitaker-Menezes D, Capparelli C, Balliet R, Lin Z, Pestell RG, Howell A, Aquila S, Andò S, Martinez-Outschoorn U, et al. Metabolic reprogramming of cancer-associated fibroblasts by TGF-ß drives tumor growth: connecting TGF-ß signaling with "Warburg-like" cancer metabolism and L-lactate production. Cell Cycle 2012; 11: 3019-35; PMID: 22874531; http://dx.doi.org/10.4161/cc.21384
127. Martinez-Outschoorn UE, Balliet RM, Lin Z, Whitaker-Menezes D, Howell A, Sotgia F, Lisanti MP. Hereditary ovarian cancer and two-compartment tumor metabolism: epithelial loss of BRCA1 induces hydrogen peroxide production, driving oxidative stress and NF?B activation in the tumor stroma. Cell Cycle 2012; 11: 4152-66; PMID: 23047606; http://dx.doi.org/10.4161/cc.22226
128. Carito V, Bonuccelli G, Martinez-Outschoorn UE, Whitaker-Menezes D, Caroleo MC, Cione E, Howell A, Pestell RG, Lisanti MP, Sotgia F. Metabolic remodeling of the tumor microenvironment: migration stimulating factor (MSF) reprograms myofibroblasts toward lactate production, fueling anabolic tumor growth. Cell Cycle 2012; 11: 3403-14; PMID: 22918248; http://dx.doi.org/10.4161/ cc.21701
129. Jin H, Sperka T, Herrlich P, Morrison H. Tumorigenic transformation by CPI-17 through inhibition of a merlin phosphatase. Nature 2006; 442: 576-9; PMID: 16885985; http://dx.doi.org/10.1038/nature04856 (Pubitemid 44167917)
130. Jin H, Wang X, Ying J, Wong AH, Cui Y, Srivastava G, Shen ZY, Li EM, Zhang Q, Jin J, et al. Epigenetic silencing of a Ca(2+)-regulated Ras
131. Lam EK, Wa ng X, Shin V Y, Zhang S, Morrison H, Sun J, et al. A microRNA contribution to aberrant Ras activation in gastric cancer. American journal of translational research 2 011; 3: 2 0 9-18.
132. Kim JH, Kim HY, Lee YK, Yoon YS, Xu WG, Yoon JK, Choi SE, Ko YG, Kim MJ, Lee SJ, et al. Involvement of mitophagy in oncogenic K-Ras-induced transformation: overcoming a cellular energy deficit from glucose deficiency. Autophagy 2011; 7: 1187-98; PMID: 21738012; http://dx.doi.org/10.4161/auto.7.10. 16643
133. Liu X, Wang X, Zhang J, Lam EK, Shin VY, Cheng AS, Yu J, Chan FK, Sung JJ, Jin HC. Warburg effect revisited: an epigenetic link between glycolysis and gastric carcinogenesis. Oncogene 2010; 29: 442-50; PMID: 19 8 81551; http://dx.doi.org/10.1038/onc.2009.332
134. Lock R, Roy S, Kenific CM, Su JS, Salas E, Ronen SM, Debnath J. Autophagy facilitates glycolysis during Ras-mediated oncogenic transformation. Mol Biol Cell 2011; 22: 165-78; PMID: 211190 05; http://dx.doi.org/10.1091/mbc.E10-06- 0500
135. Duran A, Linares JF, Galvez AS, Wikenheiser K, Flores JM, Diaz-Meco MT, Moscat J. The signaling adaptor p62 is an important NF-kappaB mediator in tumorigenesis. Cancer Cell 2008; 13: 343-54; PMID: 18394557; http://dx.doi.org/10.1016/j. ccr.2008.02.001 (Pubitemid 351446193)
136. Nicholson KM, Anderson NG. The protein kinase B/Akt signalling pathway in human malignancy. Cell Signal 2002; 14: 381-95; PMID: 11882383; http://dx.doi.org/10.1016/S0898-6568(01)00271-6 (Pubitemid 34214843)
137. Santi SA, Lee H. The Akt isoforms are present at distinct subcellular locations. Am J Physiol Cell Physiol 2010; 298:C580-91; PMID: 20018949; http://dx.doi.org/10.1152/ajpcell.00375.2009
138. Santi SA, Lee H. Ablation of Akt2 induces autophagy through cell cycle arrest, the downregulation of p70S6K, and the deregulation of mitochondria in MDA-MB231 cells. PLoS One 2011; 6:e14614; PMID: 21297943; http://dx.doi.org/10. 1371/jou r n a l. p on e.0 014 614
139. Liang XH, Jackson S, Seaman M, Brown K, Kempkes B, Hibshoosh H, Levine B. Induction of autophagy and inhibition of tumorigenesis by beclin 1. Nature 1999; 402: 672-6; PMID: 10604474; http://dx.doi.org/10.1038/45257 (Pubitemid 129516338)
140. Yue Z, Jin S, Yang C, Levine AJ, Heintz N. Beclin 1, an autophagy gene essential for early embryonic development, is a haploinsufficient tumor suppressor. Proc Natl Acad Sci U S A 2003; 100: 1507 7-82; PMID: 14657337; http://dx.doi.org/10.1073/pn a s. 2 4 3625510 0 (Pubitemid 37518019)
141. Qu X, Yu J, Bhagat G, Furuya N, Hibshoosh H, Troxel A, Rosen J, Eskelinen EL, Mizushima N, Ohsumi Y, et al. Promotion of tumorigenesis by heterozygous disruption of the beclin 1 autophagy gene. J Clin Invest 2003; 112: 1809-20; PMID: 14638851 (Pubitemid 38063704)
142. Abedin MJ, Wang D, McDonnell MA, Lehmann U, Kelekar A. Autophagy delays apoptotic death in breast cancer cells following DNA damage. Cell Death Differ 2007; 14: 500-10; PMID: 16990848; http://dx.doi.org/10.1038/sj.cdd.4402039
143. Katayama M, Kawaguchi T, Berger MS, Pieper RO. DNA damaging agent-induced autophagy produces a cytoprotective adenosine triphosphate surge in malignant glioma cells. Cell Death Differ 2007; 14: 548-58; PMID: 16946731; http://dx.doi.org/10.1038/sj.cdd.4402030
144. Karantza-Wadsworth V, Patel S, Kravchuk O, Chen G, Mathew R, Jin S, White E. Autophagy mitigates metabolic stress and genome damage in mammary tumorigenesis. Genes Dev 2007; 21: 1621-35; PMID: 17606641; http://dx.doi.org/ 10.1101/ga d.156570 7 (Pubitemid 47026367)
145. Matsunaga K, Saitoh T, Tabat a K, Omori H, Satoh T, Kurotori N, Maejima I, Shirahama-Noda K, Ichimura T, Isobe T, et al. Two Beclin 1-binding proteins, Atg14L and Rubicon, reciprocally regulate autophagy at different stages. Nat Cell Biol 2009; 11: 385-96; PMID: 19270 696; http://dx.doi.org/10.1038/ncb1846
146. Van Humbeeck C, Cornelissen T, Vandenberghe W. Ambra1: a Parkin-binding protein involved in mitophagy. Autophagy 2011; 7: 1555-6; PMID: 21921694; http://dx.doi.org/10.4161/auto.7.12.17893
147. Simonsen A, Tooze SA. Coordination of membrane events during autophagy by multiple class III PI3-kinase complexes. J Cell Biol 2009; 186: 773-82; PMID: 19797076; http://dx.doi.org/10.1083/jcb. 2 0 0 9 0 7014
148. Liang C, Feng P, Ku B, Dotan I, Canaani D, Oh BH, Jung JU. Autophagic and tumour suppressor activity of a novel Beclin1-binding protein UVRAG. Nat Cell Biol 2006; 8: 688-99; PMID: 16799551; http://dx.doi.org/10.1038/ncb1426
149. Takahashi Y, Young MM, Serfass JM, Hori T, Wang HG. Sh3glb1/Bif-1 and mitophagy: Acquisition of apoptosis resistance during Myc-driven lymphomagenesis. Autophagy 2013; 1107-9; PMID: 23680845; http://dx.doi.org/10. 4161/auto.24817
150. Takahashi Y, Coppola D, Matsushita N, Cualing HD, Sun M, Sato Y, Liang C, Jung JU, Cheng JQ, Mulé JJ, et al. Bif-1 interacts with Beclin 1 through UVRAG and regulates autophagy and tumorigenesis. Nat Cell Biol 2007; 9: 1142-51; PMID: 17891140; http://dx.doi.org/10.1038/ncb1634 (Pubitemid 47500490)
151. Knuutila S, Aalto Y, Autio K, Björkqvist AM, El-Rifai W, Hemmer S, Huhta T, Kettunen E, Kiuru-Kuhlefelt S, Larramendy ML, et al. DNA copy number losses in human neoplasms. Am J Pathol 1999; 155: 683-94; PMID: 10487825; http://dx.doi.org/10.1016/S0002-9440(10)65166-8 (Pubitemid 29426813)
152. Lee JW, Jeong EG, Soung YH, Nam SW, Lee JY, Yoo NJ, Lee SH. Decreased expression of tumour suppressor Bax-interacting factor-1 (Bif-1), a Bax activator, in gastric carcinomas. Pathology 2006; 38: 312-5; PMID: 16916719; http://dx.doi.org/10.1080/00313020600820880 (Pubitemid 44266628)
153. Coppola D, Oliveri C, Sayegh Z, Boulware D, Takahashi Y, Pow-Sang J, Djeu JY, Wang HG. Bax-interacting factor-1 expression in prostate cancer. Clin Genitourin Cancer 2008; 6: 117-21; PMID: 18824435; http://dx.doi.org/10.3816/ CGC.2008.n.018
154. Coppola D, Khalil F, Eschrich SA, Boulware D, Yeatman T, Wa ng HG. Down-regulation of Bax-interacting factor-1 in colorectal adenocarcinoma. Cancer 2008; 113: 2665-70; PMID: 18833585; http://dx.doi.org/10.1002/cncr.23892
155. Kim SY, Oh YL, Kim KM, Jeong EG, Kim MS, Yoo NJ, Lee SH. Decreased expression of Bax-interacting factor-1 (Bif-1) in invasive urinary bladder and gallbladder cancers. Pathology 2008; 40: 553-7; PMID: 18752120; http://dx.doi.org/10.1080/00313020802320440
156. Coppola D, Helm J, Ghayouri M, Malafa MP, Wa ng HG. Down-regulation of Bax-interacting factor 1 in human pancreatic ductal adenocarcinoma. Pancreas 2011; 40: 433-7; PMID: 21283040; http://dx.doi.org/10.1097/MPA.0b013e318205eb03
157. Takahashi Y, Karbowski M, Yamaguchi H, Kazi A, Wu J, Sebti SM, Youle RJ, Wang HG. Loss of Bif-1 suppresses Bax/Bak conformational change and mitochondrial apoptosis. Mol Cell Biol 2005; 25: 9369-82; PMID: 16227588; http://dx.doi.org/10.1128/MCB.25.21.9369-9382.2005 (Pubitemid 41507838)
158. Takahashi Y, Hori T, Cooper TK, Liao J, Desai N, Serfass JM, Young MM, Park S, Izu Y, Wang HG. Bif-1 haploinsufficiency promotes chromosomal instability and accelerates Myc-driven lymphomagenesis via suppression of mitophagy. Blood 2013; 121: 1622-32; PMID: 23287860; http://dx.doi.org/10.1182/ blood-2012-10-459826
159. Cuddeback SM, Yamaguchi H, Komatsu K, Miyashita T, Yamada M, Wu C, Singh S, Wang HG. Molecular cloning and characterization of Bif-1. A novel Src homology 3 domain-containing protein that associates with Bax. J Biol Chem 2001; 276: 20559-65; PMID: 11259440; http://dx.doi.org/10.1074/jbc. M1015272 0 0
160. Fimia GM, Stoykova A, Romagnoli A, Giunta L, Di Bartolomeo S, Nardacci R, Corazzari M, Fuoco C, Ucar A, Schwartz P, et al. Ambra1 regulates autophagy and development of the nervous system. Nature 2007; 447: 1121-5; PMID: 17589504 (Pubitemid 47014434)
161. Strappazzon F, Vietri-Rudan M, Campello S, Nazio F, Florenzano F, Fimia GM, Piacentini M, Levine B, Cecconi F. Mitochondrial BCL-2 inhibits AMBRA1-induced autophagy. EMBO J 2011; 30: 1195-208; PMID: 21358617; http://dx.doi.org/10.1038/emboj.2011.49
162. Fimia GM, Corazzari M, Antonioli M, Piacentini M. Ambra1 at the crossroad between autophagy and cell death. Oncogene 2013; 32: 3 3 11-8; PMID: 23069654; http://dx.doi.org/10.1038/onc.2012.455
163. Van Humbeeck C, Cornelissen T, Hofkens H, Mandemakers W, Gevaert K, De Strooper B, et al. Parkin interacts with Ambra1 to induce mitophagy. The Journal of neuroscience: the official journal of the Society for Neuroscience 2011; 31: 10249-61.
164. Burton TR, Gibson SB. The role of Bcl-2 family member BNIP3 in cell death and disease: NIPping at the heels of cell death. Cell Death Differ 2009; 16: 515-23; PMID: 19136941; http://dx.doi.org/10.1038/cdd.2008.185
165. Zhu Y, Massen S, Te r e n z i o M, Lang V, Chen-Lindner S, Eils R, Novak I, Dikic I, Hamacher-Brady A, Brady NR. Modulation of serines 17 and 24 in the LC3-interacting region of Bnip3 determines pro-survival mitophagy versus apoptosis. J Biol Chem 2013; 288: 1099-113; PMID: 23209295; http://dx.doi.org/ 10.1074/jbc.M112.399345
166. Zhang J, Ney PA. Role of BNIP3 and NIX in cell death, autophagy, and mitophagy. Cell Death Differ 2009; 16: 939-46; PMID: 19229244; http://dx.doi.org/10.1038/cdd.2009.16
167. Thomas RL, Kubli DA, Gustafsson AB. Bnip3-mediated defects in oxidative phosphorylation promote mitophagy. Autophagy 2011; 7: 775-7; PMID: 21460627; http://dx.doi.org/10.4161/auto.7.7.1553 6
168. Kondo Y, Kondo S. Autophagy and cancer therapy. Autophagy 2006; 2: 85-90; PMID: 16874083
169. Gargini R, García-Escudero V, Izquierdo M. Therapy mediated by mitophagy abrogates tumor progression. Autophagy 2 011; 7: 466-76; PMID: 21270513; http://dx.doi.org/10.4161/auto.7.5.14731
170. García-Escudero V, Gargini R, Izquierdo M. Glioma regression in vitro and in vivo by a suicide combined treatment. Mol Cancer Res 2008; 6: 407-17; PMID: 18337448; h t t p://d x. d o i. o r g/10.115 8/15 4 1-7786.MCR-07-0243 (Pubitemid 351416531)
171. García-Escudero V, Gargini R. Autophagy induction as an efficient strategy to eradicate tumors. Autophagy 2008; 4: 923-5; PMID: 18716458
172. Girald W, Collin A, Izquierdo M. Toxicity and delivery methods for the linamarase/linamarin/glucose oxidase system, when used against human glioma tumors implanted in the brain of nude rats. Cancer Lett 2011; 313: 99-107; PMID: 21955616; http://dx.doi.org/10.1016/j.canlet.2011.08.029
173. Cortés ML, García-Escudero V, Hughes M, Izquierdo M. Cyanide bystander effect of the linamarase/linamarin killer-suicide gene therapy system. J Gene Med 2002; 4: 407-14; PMID: 12124983; http://dx.doi.org/10.1002/ jgm.280 (Pubitemid 40277178)
174. Adan-Gokbulut A, Kartal-Yandim M, Iskender G, Baran Y. Novel agents targeting bioactive sphingolipids for the treatment of cancer. Curr Med Chem 2013; 20: 108-22; PMID: 23244584
175. Rego A, Costa M, Chaves SR, Matmati N, Pereira H, Sousa MJ, Moradas-Ferreira P, Hannun YA, Costa V, Côrte-Real M. Modulation of mitochondrial outer membrane permeabilization and apoptosis by ceramide metabolism. PLoS One 2012; 7:e48571; PMID: 23226203; http://dx.doi.org/10.1371/ journal.pone.0048571
176. Saddoughi SA, Ogretmen B. Diverse functions of ceramide in cancer cell death and proliferation. Adv Cancer Res 2013; 117: 37-58; PMID: 23290776
177. Venkataraman K, Riebeling C, Bodennec J, Riezman H, Allegood JC, Sullards MC, Merrill AH Jr., Futerman AH. Upstream of growth and differentiation factor 1 (uog1), a mammalian homolog of the yeast longevity assurance gene 1 (LAG1), regulates N-stearoyl-sphinganine (C18-(dihydro)ceramide) synthesis in a fumonisin B1-independent manner in mammalian cells. J Biol Chem 2002; 277: 35642-9; PMID: 12105227; http://dx.doi.org/10.1074/jbc.M205211200
178. Saddoughi SA, Garrett-Mayer E, Chaudhary U, O'Brien PE, Afrin LB, Day TA, Gillespie MB, Sharma AK, Wilhoit CS, Bostick R, et al. Results of a phase II trial of gemcitabine plus doxorubicin in patients with recurrent head and neck cancers: serum C18-ceramide as a novel biomarker for monitoring response. Clin Cancer Res 2011; 17: 6097-105; PMID: 21791630; http://dx.doi.org/10.1158/1078- 0432.CCR-11-0930
179. Wang X, Leung AW, Luo J, Xu C. TEM observation of ultrasound-induced mitophagy in nasopharyngeal carcinoma cells in the presence of curcumin. Exp Ther Med 2012; 3: 146-8; PMID: 22969860
180. Huh WK, Falvo J V, Gerke LC, Carroll AS, Howson RW, Weissman JS, O'Shea EK. Global analysis of protein localization in budding yeast. Nature 2003; 425: 686-91; PMID: 14562095; http://dx.doi.org/10.1038/nature02026 (Pubitemid 37314307)
181. Bell C, English L, Boulais J, Chemali M, Caron-Lizotte O, Desjardins M, Thibault P. Quantitative Proteomics Reveals the Induction of Mitophagy in Tumor Necrosis Factor-a-activated (TNFa) Macrophages. Mol Cell Proteomics 2013; 12: 2394-407; PMID: 23674617; http://dx.doi.org/10.1074/mcp.M112.025775.
182. Jangamreddy JR, Ghavami S, Grabarek J, Kratz G, Wiechec E, Fredriksson BA, et al. Salinomycin induces activation of autophagy, mitophagy and affects mitochondrial polarity: Differences between primary and cancer cells. Biochim Biophys Acta 2013; 1832: 2057-69
183. Wurm CA, Neumann D, Lauterbach MA, Harke B, Egner A, Hell SW, Jakobs S. Nanoscale distribution of mitochondrial import receptor Tom20 is adjusted to cellular conditions and exhibits an inner-cellular gradient. Proc Natl Acad Sci U S A 2011; 108: 13546-51; PMID: 2179 9113; http://dx.doi.org/10.1073/pnas. 1107553108
184. Lupfer C, Thomas PG, Anand PK, Vogel P, Milasta S, Martinez J, Huang G, Green M, Kundu M, Chi H, et al. Receptor interacting protein kinase 2-mediated mitophagy regulates inflammasome activation during virus infection. Nat Immunol 2013; 14: 480-8; PMID: 23525089; http://dx.doi.org/10.1038/ni.2563