Mitochondrial Alteration: A Major Player in Carcinogenesis
Cell Biology
Volume 3, Issue 2-1, April 2015, Pages: 8-16
Received: Jan. 28, 2015; Accepted: Jan. 28, 2015; Published: Feb. 10, 2015
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Lokendra Kumar Sharma, Biotechnology Program, Centre for Biological Sciences, Central University of Bihar, Patna, Bihar, India
Meenakshi Tiwari, Department of Laboratory Medicine and Pathology, All India Institute of Medical Sciences Patna, Bihar, India
Santosh Kumar Mishra, Biotechnology Program, Centre for Biological Sciences, Central University of Bihar, Patna, Bihar, India
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In recent years we have witnessed mounting evidences on how a normal cell changes its cellular signaling and metabolic pathways to become highly proliferative cancer cell. Since mitochondrion is a major hub of energy production and several metabolic pathways, it is taking the center stage in defining alterations in energy homeostasis and metabolic rerouting of cancer cell proliferation. Similarly, mutations in the mitochondrial genome in cancer are providing new insights on how these mutations affect mitochondrial functions and change the oncogenic signaling and apoptosis mechanism. In this review, we will summarize these important mitochondrial mechanisms that contribute significantly in the progression of cancer. Further therapeutic approaches targeted to these altered mitochondrial mechanism in cancer are discussed. This review is a part of special issue on Mitochondria: implications in human health and diseases.
Mitochondria, Metabolism, Reactive Oxygen Species and Cancer
To cite this article
Lokendra Kumar Sharma, Meenakshi Tiwari, Santosh Kumar Mishra, Mitochondrial Alteration: A Major Player in Carcinogenesis, Cell Biology. Special Issue: Mitochondria: Implications in Human Health and Diseases. Vol. 3, No. 2-1, 2015, pp. 8-16. doi: 10.11648/j.cb.s.2015030201.12
D. C. Wallace, A mitochondrial paradigm of metabolic and degenerative diseases, aging, and cancer: a dawn for evolutionary medicine, Annual review of genetics, 39 (2005) 359-407.
B. N. Ames, M. K. Shigenaga, Oxidants are a major contributor to aging, Annals of the New York Academy of Sciences, 663 (1992) 85-96.
D. Harman, Role of free radicals in aging and disease, Annals of the New York Academy of Sciences, 673 (1992) 126-141.
A. Chatterjee, E. Mambo, D. Sidransky, Mitochondrial DNA mutations in human cancer, Oncogene, 25 (2006) 4663-4674.
O. Warburg, F. Wind, E. Negelein, The Metabolism of Tumors in the Body, The Journal of general physiology, 8 (1927) 519-530.
O. Warburg, On respiratory impairment in cancer cells, Science, 124 (1956) 269-270.
P.L. Pedersen, Tumor mitochondria and the bioenergetics of cancer cells, Progress in experimental tumor research, 22 (1978) 190-274.
S. Weinhouse, The Warburg hypothesis fifty years later, Zeitschrift fur Krebsforschung und klinische Onkologie. Cancer research and clinical oncology, 87 (1976) 115-126.
F. Weinberg, R. Hamanaka, W.W. Wheaton, S. Weinberg, J. Joseph, M. Lopez, B. Kalyanaraman, G.M. Mutlu, G.R. Budinger, N.S. Chandel, Mitochondrial metabolism and ROS generation are essential for Kras-mediated tumorigenicity, Proceedings of the National Academy of Sciences of the United States of America, 107 (2010) 8788-8793.
R. Moreno-Sanchez, S. Rodriguez-Enriquez, A. Marin-Hernandez, E. Saavedra, Energy metabolism in tumor cells, The FEBS journal, 274 (2007) 1393-1418.
J.W. Locasale, A.R. Grassian, T. Melman, C.A. Lyssiotis, K.R. Mattaini, A.J. Bass, G. Heffron, C.M. Metallo, T. Muranen, H. Sharfi, A.T. Sasaki, D. Anastasiou, E. Mullarky, N.I. Vokes, M. Sasaki, R. Beroukhim, G. Stephanopoulos, A.H. Ligon, M. Meyerson, A.L. Richardson, L. Chin, G. Wagner, J.M. Asara, J.S. Brugge, L.C. Cantley, M.G. Vander Heiden, Phosphoglycerate dehydrogenase diverts glycolytic flux and contributes to oncogenesis, Nature genetics, 43 (2011) 869-874.
R. Possemato, K.M. Marks, Y.D. Shaul, M.E. Pacold, D. Kim, K. Birsoy, S. Sethumadhavan, H.K. Woo, H.G. Jang, A.K. Jha, W.W. Chen, F.G. Barrett, N. Stransky, Z.Y. Tsun, G.S. Cowley, J. Barretina, N.Y. Kalaany, P.P. Hsu, K. Ottina, A.M. Chan, B. Yuan, L.A. Garraway, D.E. Root, M. Mino-Kenudson, E.F. Brachtel, E.M. Driggers, D.M. Sabatini, Functional genomics reveal that the serine synthesis pathway is essential in breast cancer, Nature, 476 (2011) 346-350.
T. Hitosugi, L. Zhou, S. Elf, J. Fan, H.B. Kang, J.H. Seo, C. Shan, Q. Dai, L. Zhang, J. Xie, T.L. Gu, P. Jin, M. Aleckovic, G. LeRoy, Y. Kang, J.A. Sudderth, R.J. DeBerardinis, C.H. Luan, G.Z. Chen, S. Muller, D.M. Shin, T.K. Owonikoko, S. Lonial, M.L. Arellano, H.J. Khoury, F.R. Khuri, B.H. Lee, K. Ye, T.J. Boggon, S. Kang, C. He, J. Chen, Phosphoglycerate mutase 1 coordinates glycolysis and biosynthesis to promote tumor growth, Cancer cell, 22 (2012) 585-600.
G. L. Semenza, HIF-1: upstream and downstream of cancer metabolism, Current opinion in genetics & development, 20 (2010) 51-56.
G. Qing, N. Skuli, P.A. Mayes, B. Pawel, D. Martinez, J.M. Maris, M.C. Simon, Combinatorial regulation of neuroblastoma tumor progression by N-Myc and hypoxia inducible factor HIF-1alpha, Cancer research, 70 (2010) 10351-10361.
R.L. Elstrom, D.E. Bauer, M. Buzzai, R. Karnauskas, M.H. Harris, D.R. Plas, H. Zhuang, R.M. Cinalli, A. Alavi, C.M. Rudin, C.B. Thompson, Akt stimulates aerobic glycolysis in cancer cells, Cancer research, 64 (2004) 3892-3899.
S.Y. Lunt, M.G. Vander Heiden, Aerobic glycolysis: meeting the metabolic requirements of cell proliferation, Annual review of cell and developmental biology, 27 (2011) 441-464.
B.E. Baysal, R.E. Ferrell, J.E. Willett-Brozick, E.C. Lawrence, D. Myssiorek, A. Bosch, A. van der Mey, P.E. Taschner, W.S. Rubinstein, E.N. Myers, C.W. Richard, 3rd, C.J. Cornelisse, P. Devilee, B. Devlin, Mutations in SDHD, a mitochondrial complex II gene, in hereditary paraganglioma, Science, 287 (2000) 848-851.
I. P. Tomlinson, N. A. Alam, A. J. Rowan, E. Barclay, E. E. Jaeger, D. Kelsell, I. Leigh, P. Gorman, H. Lamlum, S. Rahman, R. R. Roylance, S. Olpin, S. Bevan, K. Barker, N. Hearle, R. S. Houlston, M. Kiuru, R. Lehtonen, A. Karhu, S. Vilkki, P. Laiho, C. Eklund, O. Vierimaa, K. Aittomaki, M. Hietala, P. Sistonen, A. Paetau, R. Salovaara, R. Herva, V. Launonen, L. A. Aaltonen, C. Multiple Leiomyoma, Germline mutations in FH predispose to dominantly inherited uterine fibroids, skin leiomyomata and papillary renal cell cancer, Nature genetics, 30 (2002) 406-410.
H. Yan, D. W. Parsons, G. Jin, R. McLendon, B. A. Rasheed, W. Yuan, I. Kos, I. Batinic-Haberle, S. Jones, G. J. Riggins, H. Friedman, A. Friedman, D. Reardon, J. Herndon, K. W. Kinzler, V. E. Velculescu, B. Vogelstein, D. D. Bigner, IDH1 and IDH2 mutations in gliomas, The New England journal of medicine, 360 (2009) 765-773.
L. Dang, D. W. White, S. Gross, B. D. Bennett, M. A. Bittinger, E. M. Driggers, V. R. Fantin, H. G. Jang, S. Jin, M. C. Keenan, K. M. Marks, R. M. Prins, P. S. Ward, K. E. Yen, L. M. Liau, J. D. Rabinowitz, L. C. Cantley, C. B. Thompson, M. G. Vander Heiden, S. M. Su, Cancer-associated IDH1 mutations produce 2-hydroxyglutarate, Nature, 462 (2009) 739-744.
L. B. Sullivan, N. S. Chandel, Mitochondrial metabolism in TCA cycle mutant cancer cells, Cell cycle, 13 (2014) 347-348.
A. R. Mullen, W. W. Wheaton, E. S. Jin, P. H. Chen, L. B. Sullivan, T. Cheng, Y. Yang, W. M. Linehan, N. S. Chandel, R. J. DeBerardinis, Reductive carboxylation supports growth in tumour cells with defective mitochondria, Nature, 481 (2012) 385-388.
C. T. Hensley, A. T. Wasti, R. J. DeBerardinis, Glutamine and cancer: cell biology, physiology, and clinical opportunities, The Journal of clinical investigation, 123 (2013) 3678-3684.
M. Jain, R. Nilsson, S. Sharma, N. Madhusudhan, T. Kitami, A.L. Souza, R. Kafri, M.W. Kirschner, C.B. Clish, V.K. Mootha, Metabolite profiling identifies a key role for glycine in rapid cancer cell proliferation, Science, 336 (2012) 1040-1044.
E. Currie, A. Schulze, R. Zechner, T.C. Walther, R.V. Farese, Jr., Cellular fatty acid metabolism and cancer, Cell metabolism, 18 (2013) 153-161.
S. Anderson, A.T. Bankier, B.G. Barrell, M.H. de Bruijn, A.R. Coulson, J. Drouin, I.C. Eperon, D.P. Nierlich, B.A. Roe, F. Sanger, P.H. Schreier, A.J. Smith, R. Staden, I.G. Young, Sequence and organization of the human mitochondrial genome, Nature, 290 (1981) 457-465.
K. Polyak, Y. Li, H. Zhu, C. Lengauer, J.K. Willson, S.D. Markowitz, M.A. Trush, K.W. Kinzler, B. Vogelstein, Somatic mutations of the mitochondrial genome in human colorectal tumours, Nature genetics, 20 (1998) 291-293.
J. Lu, L.K. Sharma, Y. Bai, Implications of mitochondrial DNA mutations and mitochondrial dysfunction in tumorigenesis, Cell research, 19 (2009) 802-815.
M. P. King, G. Attardi, Human cells lacking mtDNA: repopulation with exogenous mitochondria by complementation, Science, 246 (1989) 500-503.
Y. Shidara, K. Yamagata, T. Kanamori, K. Nakano, J.Q. Kwong, G. Manfredi, H. Oda, S. Ohta, Positive contribution of pathogenic mutations in the mitochondrial genome to the promotion of cancer by prevention from apoptosis, Cancer research, 65 (2005) 1655-1663.
J. A. Petros, A.K. Baumann, E. Ruiz-Pesini, M.B. Amin, C.Q. Sun, J. Hall, S. Lim, M.M. Issa, W.D. Flanders, S.H. Hosseini, F.F. Marshall, D.C. Wallace, mtDNA mutations increase tumorigenicity in prostate cancer, Proceedings of the National Academy of Sciences of the United States of America, 102 (2005) 719-724.
J.S. Park, L.K. Sharma, H. Li, R. Xiang, D. Holstein, J. Wu, J. Lechleiter, S.L. Naylor, J.J. Deng, J. Lu, Y. Bai, A heteroplasmic, not homoplasmic, mitochondrial DNA mutation promotes tumorigenesis via alteration in reactive oxygen species generation and apoptosis, Human molecular genetics, 18 (2009) 1578-1589.
L.K. Sharma, H. Fang, J. Liu, R. Vartak, J. Deng, Y. Bai, Mitochondrial respiratory complex I dysfunction promotes tumorigenesis through ROS alteration and AKT activation, Human molecular genetics, 20 (2011) 4605-4616.
K. Ishikawa, K. Takenaga, M. Akimoto, N. Koshikawa, A. Yamaguchi, H. Imanishi, K. Nakada, Y. Honma, J. Hayashi, ROS-generating mitochondrial DNA mutations can regulate tumor cell metastasis, Science, 320 (2008) 661-664.
R.S. Arnold, C.Q. Sun, J.C. Richards, G. Grigoriev, I.M. Coleman, P.S. Nelson, C.L. Hsieh, J.K. Lee, Z. Xu, A. Rogatko, A.O. Osunkoya, M. Zayzafoon, L. Chung, J.A. Petros, Mitochondrial DNA mutation stimulates prostate cancer growth in bone stromal environment, The Prostate, 69 (2009) 1-11.
K. Ishikawa, N. Koshikawa, K. Takenaga, K. Nakada, J. Hayashi, Reversible regulation of metastasis by ROS-generating mtDNA mutations, Mitochondrion, 8 (2008) 339-344.
M. Kulawiec, K.M. Owens, K.K. Singh, Cancer cell mitochondria confer apoptosis resistance and promote metastasis, Cancer biology & therapy, 8 (2009) 1378-1385.
G.L. Semenza, Hypoxia-inducible factors in physiology and medicine, Cell, 148 (2012) 399-408.
H. Zhang, P. Gao, R. Fukuda, G. Kumar, B. Krishnamachary, K.I. Zeller, C.V. Dang, G.L. Semenza, HIF-1 inhibits mitochondrial biogenesis and cellular respiration in VHL-deficient renal cell carcinoma by repression of C-MYC activity, Cancer cell, 11 (2007) 407-420.
F. Li, Y. Wang, K.I. Zeller, J.J. Potter, D.R. Wonsey, K.A. O'Donnell, J.W. Kim, J.T. Yustein, L.A. Lee, C.V. Dang, Myc stimulates nuclearly encoded mitochondrial genes and mitochondrial biogenesis, Molecular and cellular biology, 25 (2005) 6225-6234.
J.W. Kim, I. Tchernyshyov, G.L. Semenza, C.V. Dang, HIF-1-mediated expression of pyruvate dehydrogenase kinase: a metabolic switch required for cellular adaptation to hypoxia, Cell metabolism, 3 (2006) 177-185.
I. Papandreou, R.A. Cairns, L. Fontana, A.L. Lim, N.C. Denko, HIF-1 mediates adaptation to hypoxia by actively downregulating mitochondrial oxygen consumption, Cell metabolism, 3 (2006) 187-197.
R. Fukuda, H. Zhang, J.W. Kim, L. Shimoda, C.V. Dang, G.L. Semenza, HIF-1 regulates cytochrome oxidase subunits to optimize efficiency of respiration in hypoxic cells, Cell, 129 (2007) 111-122.
H. Pelicano, R.H. Xu, M. Du, L. Feng, R. Sasaki, J.S. Carew, Y. Hu, L. Ramdas, L. Hu, M.J. Keating, W. Zhang, W. Plunkett, P. Huang, Mitochondrial respiration defects in cancer cells cause activation of Akt survival pathway through a redox-mediated mechanism, The Journal of cell biology, 175 (2006) 913-923.
R.B. Robey, N. Hay, Mitochondrial hexokinases, novel mediators of the antiapoptotic effects of growth factors and Akt, Oncogene, 25 (2006) 4683-4696.
K. Bensaad, A. Tsuruta, M.A. Selak, M.N. Vidal, K. Nakano, R. Bartrons, E. Gottlieb, K.H. Vousden, TIGAR, a p53-inducible regulator of glycolysis and apoptosis, Cell, 126 (2006) 107-120.
S. Matoba, J.G. Kang, W.D. Patino, A. Wragg, M. Boehm, O. Gavrilova, P.J. Hurley, F. Bunz, P.M. Hwang, p53 regulates mitochondrial respiration, Science, 312 (2006) 1650-1653.
J.Q. Kwong, M.S. Henning, A.A. Starkov, G. Manfredi, The mitochondrial respiratory chain is a modulator of apoptosis, The Journal of cell biology, 179 (2007) 1163-1177.
M. Ott, V. Gogvadze, S. Orrenius, B. Zhivotovsky, Mitochondria, oxidative stress and cell death, Apoptosis : an international journal on programmed cell death, 12 (2007) 913-922.
I.R. Indran, G. Tufo, S. Pervaiz, C. Brenner, Recent advances in apoptosis, mitochondria and drug resistance in cancer cells, Biochimica et biophysica acta, 1807 (2011) 735-745.
A.F. Santidrian, A. Matsuno-Yagi, M. Ritland, B.B. Seo, S.E. LeBoeuf, L.J. Gay, T. Yagi, B. Felding-Habermann, Mitochondrial complex I activity and NAD+/NADH balance regulate breast cancer progression, The Journal of clinical investigation, 123 (2013) 1068-1081.
R.A. Butow, N.G. Avadhani, Mitochondrial signaling: the retrograde response, Molecular cell, 14 (2004) 1-15.
T. Arnould, S. Vankoningsloo, P. Renard, A. Houbion, N. Ninane, C. Demazy, J. Remacle, M. Raes, CREB activation induced by mitochondrial dysfunction is a new signaling pathway that impairs cell proliferation, The EMBO journal, 21 (2002) 53-63.
D. Freyssenet, I. Irrcher, M.K. Connor, M. Di Carlo, D.A. Hood, Calcium-regulated changes in mitochondrial phenotype in skeletal muscle cells, American journal of physiology. Cell physiology, 286 (2004) C1053-1061.
F. Celsi, P. Pizzo, M. Brini, S. Leo, C. Fotino, P. Pinton, R. Rizzuto, Mitochondria, calcium and cell death: a deadly triad in neurodegeneration, Biochimica et biophysica acta, 1787 (2009) 335-344.
H. Pelicano, D.S. Martin, R.H. Xu, P. Huang, Glycolysis inhibition for anticancer treatment, Oncogene, 25 (2006) 4633-4646.
J.G. Pastorino, J.B. Hoek, N. Shulga, Activation of glycogen synthase kinase 3beta disrupts the binding of hexokinase II to mitochondria by phosphorylating voltage-dependent anion channel and potentiates chemotherapy-induced cytotoxicity, Cancer research, 65 (2005) 10545-10554.
S. Bonnet, S.L. Archer, J. Allalunis-Turner, A. Haromy, C. Beaulieu, R. Thompson, C.T. Lee, G.D. Lopaschuk, L. Puttagunta, S. Bonnet, G. Harry, K. Hashimoto, C.J. Porter, M.A. Andrade, B. Thebaud, E.D. Michelakis, A mitochondria-K+ channel axis is suppressed in cancer and its normalization promotes apoptosis and inhibits cancer growth, Cancer cell, 11 (2007) 37-51.
V.R. Fantin, J. St-Pierre, P. Leder, Attenuation of LDH-A expression uncovers a link between glycolysis, mitochondrial physiology, and tumor maintenance, Cancer cell, 9 (2006) 425-434.
G. Hatzivassiliou, F. Zhao, D.E. Bauer, C. Andreadis, A.N. Shaw, D. Dhanak, S.R. Hingorani, D.A. Tuveson, C.B. Thompson, ATP citrate lyase inhibition can suppress tumor cell growth, Cancer cell, 8 (2005) 311-321.
J. B. Wang, J. W. Erickson, R. Fuji, S. Ramachandran, P. Gao, R. Dinavahi, K.F. Wilson, A.L. Ambrosio, S.M. Dias, C.V. Dang, R.A. Cerione, Targeting mitochondrial glutaminase activity inhibits oncogenic transformation, Cancer cell, 18 (2010) 207-219.
C. V. Dang, MYC, metabolism, cell growth, and tumorigenesis, Cold Spring Harbor perspectives in medicine, 3 (2013).
J. A. Graves, Y. Wang, S. Sims-Lucas, E. Cherok, K. Rothermund, M.F. Branca, J. Elster, D. Beer-Stolz, B. Van Houten, J. Vockley, E.V. Prochownik, Mitochondrial structure, function and dynamics are temporally controlled by c-Myc, PloS one, 7 (2012) e37699.
S. Fletcher, E.V. Prochownik, Small-molecule inhibitors of the Myc oncoprotein, Biochimica et biophysica acta, (2014).
L. Raj, T. Ide, A.U. Gurkar, M. Foley, M. Schenone, X. Li, N.J. Tolliday, T.R. Golub, S.A. Carr, A.F. Shamji, A.M. Stern, A. Mandinova, S.L. Schreiber, S.W. Lee, Selective killing of cancer cells by a small molecule targeting the stress response to ROS, Nature, 475 (2011) 231-234.
D. Trachootham, J. Alexandre, P. Huang, Targeting cancer cells by ROS-mediated mechanisms: a radical therapeutic approach?, Nature reviews. Drug discovery, 8 (2009) 579-591.
G. Chen, F. Wang, D. Trachootham, P. Huang, Preferential killing of cancer cells with mitochondrial dysfunction by natural compounds, Mitochondrion, 10 (2010) 614-625.
C. Cerella, F. Radogna, M. Dicato, M. Diederich, Natural compounds as regulators of the cancer cell metabolism, International journal of cell biology, 2013 (2013) 639401.
R.A. Smith, M.P. Murphy, Mitochondria-targeted antioxidants as therapies, Discovery medicine, 11 (2011) 106-114.
L. Galluzzi, G. Kroemer, Mitochondrial apoptosis without VDAC, Nature cell biology, 9 (2007) 487-489.
J.E. Kokoszka, K.G. Waymire, S.E. Levy, J.E. Sligh, J. Cai, D.P. Jones, G.R. MacGregor, D.C. Wallace, The ADP/ATP translocator is not essential for the mitochondrial permeability transition pore, Nature, 427 (2004) 461-465.
T. Yagi, B.B. Seo, E. Nakamaru-Ogiso, M. Marella, J. Barber-Singh, T. Yamashita, M.C. Kao, A. Matsuno-Yagi, Can a single subunit yeast NADH dehydrogenase (Ndi1) remedy diseases caused by respiratory complex I defects?, Rejuvenation research, 9 (2006) 191-197.
J.J. Lemasters, Selective mitochondrial autophagy, or mitophagy, as a targeted defense against oxidative stress, mitochondrial dysfunction, and aging, Rejuvenation research, 8 (2005) 3-5.
K. Degenhardt, R. Mathew, B. Beaudoin, K. Bray, D. Anderson, G. Chen, C. Mukherjee, Y. Shi, C. Gelinas, Y. Fan, D.A. Nelson, S. Jin, E. White, Autophagy promotes tumor cell survival and restricts necrosis, inflammation, and tumorigenesis, Cancer cell, 10 (2006) 51-64.
S. Pavlides, I. Vera, R. Gandara, S. Sneddon, R.G. Pestell, I. Mercier, U.E. Martinez-Outschoorn, D. Whitaker-Menezes, A. Howell, F. Sotgia, M.P. Lisanti, Warburg meets autophagy: cancer-associated fibroblasts accelerate tumor growth and metastasis via oxidative stress, mitophagy, and aerobic glycolysis, Antioxidants & redox signaling, 16 (2012) 1264-1284.
J. H. Kim, H. Y. Kim, Y. K. Lee, Y.S. Yoon, W. G. Xu, J.K. Yoon, S.E. Choi, Y.G. Ko, M.J. Kim, S.J. Lee, H. J. Wang, G. Yoon, Involvement of mitophagy in oncogenic K-Ras-induced transformation: overcoming a cellular energy deficit from glucose deficiency, Autophagy, 7 (2011) 1187-1198.
S. Yang, X. Wang, G. Contino, M. Liesa, E. Sahin, H. Ying, A. Bause, Y. Li, J.M. Stommel, G. Dell'antonio, J. Mautner, G. Tonon, M. Haigis, O.S. Shirihai, C. Doglioni, N. Bardeesy, A.C. Kimmelman, Pancreatic cancers require autophagy for tumor growth, Genes & development, 25 (2011) 717-729.
Z. J. Yang, C.E. Chee, S. Huang, F.A. Sinicrope, The role of autophagy in cancer: therapeutic implications, Molecular cancer therapeutics, 10 (2011) 1533-1541.
R. Mathew, C.M. Karp, B. Beaudoin, N. Vuong, G. Chen, H.Y. Chen, K. Bray, A. Reddy, G. Bhanot, C. Gelinas, R.S. Dipaola, V. Karantza-Wadsworth, E. White, Autophagy suppresses tumorigenesis through elimination of p62, Cell, 137 (2009) 1062-1075.
R. Scherz-Shouval, Z. Elazar, Regulation of autophagy by ROS: physiology and pathology, Trends in biochemical sciences, 36 (2011) 30-38.
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