Browse > Article
http://dx.doi.org/10.5352/JLS.2019.29.9.1034

Mitochondrial Dysfunction and Cancer  

Han, Yu-Seon (Department of Molecular Biology, College of Natural Science, Pusan National University)
Jegal, Myeong-Eun (Department of Molecular Biology, College of Natural Science, Pusan National University)
Kim, Yung-Jin (Department of Molecular Biology, College of Natural Science, Pusan National University)
Publication Information
Journal of Life Science / v.29, no.9, 2019 , pp. 1034-1046 More about this Journal
Abstract
The mitochondria is the major cellular organelle of energy metabolism for the supply of cellular energy; it also plays an important role in controlling calcium regulation, reactive oxygen species (ROS) production, and apoptosis. Mitochondrial dysfunction causes various diseases, such as neurodegenerative diseases, Lou Gehrig's disease, cardiovascular disease, mental disorders, diabetes, and cancer. Most of the diseases are age-related diseases. In this review, we focus on the roles of mitochondrial dysfunction in cancer. Mitochondrial dysfunction induces carcinogenesis and is found in many cancers. The factors that cause mitochondrial dysfunction differ depending on the types of carcinoma, and those factors could cause cancer malignancy, such as resistance to therapy and metastasis. Mitochondrial dysfunction is caused by a lack of mitochondria, an inability to provide key substances, or a dysfunction in the ATP synthesis machinery. The main factor associated with cancer malignancy is mtDNA depletion. Mitochondrial dysfunction would leads to malignancy through changes in molecular activity or expression, but it is not known in detail which changes lead to cancer malignancy. In order to explore the relationship between mitochondrial dysfunction and cancer malignancy in detail, mitochondria dysfunctional cell lines are constructed using chemical methods such as EtBr treatment or gene editing methods, including shRNA and CRISPR/Cas9. Those mitochondria dysfunctional cell lines are used in the study of various diseases caused by mitochondrial dysfunction, including cancer.
Keywords
Cancer; metastasis; mitochondria; mitochondrial dysfunction; therapy resistance;
Citations & Related Records
Times Cited By KSCI : 1  (Citation Analysis)
연도 인용수 순위
1 Anderson, S., Bankier, A. T., Barrell, B. G., de Bruijn, M. H., Coulson, A. R., Drouin, J., Eperon, I. C., Nierlich, D. P., Roe, B. A., Sanger, F., Schreier, P. H., Smith, A. J., Staden, R. and Young, I. G. 1981. Sequence and organization of the human mitochondrial genome. Nature 290, 457-465.   DOI
2 Ashida, H., Mimuro, H., Ogawa, M., Kobayashi, T., Sasakawa, C., Sanada, T. and Kim, M. 2011. Cell death and infection: A double-edged sword for host and pathogen survival. J. Cell. Biol. 195, 931-942.   DOI
3 Aw, T. Y. and Jones, D. P. 1989. Nutrient supply and mitochondrial function. Annu. Rev. Nutr. 9, 229-251.   DOI
4 Bacman, S. R., Williams, S. L., Pinto, M., Peralta, S. and Moraes, C. T. 2013. Specific elimination of mutant mitochondrial genomes in patient-derived cells by mitoTALENs. Nat. Med. 19, 1111-1113.   DOI
5 Rabinovich, R. A. and Vilaro, J. 2010. Structural and functional changes of peripheral muscles in chronic obstructive pulmonary disease patients. Curr. Opin. Pulm. Med. 16, 123-133.   DOI
6 Reddy, P. H. 2008. Mitochondrial medicine for aging and neurodegenerative diseases. Neuromolecular. Med. 10, 291-315.   DOI
7 Rohr, H. P., Wacker, M. and Pein, A. V. 1976. Ethidium bromide and hepatic mitochondrial structure in mice. A morphometric analysis. Pathol. Eur. 11, 129-135.
8 Semenza, G. L. 2012. Hypoxia-inducible factors: mediators of cancer progression and targets for cancer therapy. Trends. Pharmacol. Sci. 33, 207-214.   DOI
9 Shigenaga, M. K., Hagen, T. M. and Ames, B. N. 1994. Oxidative damage and mitochondrial decay in aging. Proc. Natl. Acad. Sci. USA. 91, 10771-10778.   DOI
10 Shin, Y. K., Yoo, B. C., Chang, H. J., Jeon, E., Hong, S. H., Jung, M. S., Lim, S. J. and Park, J. G. 2005. Down-regulation of mitochondrial F1F0-ATP synthase in human colon cancer cells with induced 5-fluorouracil resistance. Cancer Res. 65, 3162-3170.   DOI
11 Sies, H. 1993. Strategies of antioxidant defense. Eur. J. Biochem. 215, 213-219.   DOI
12 Singh, K. K., Ayyasamy, V., Owens, K. M., Vujcic, M. and Koul, M. S. 2009. Mutations in mitochondrial DNA polymerase-${\gamma}$ promote breast tumorigenesis. J. Hum. Genet. 54, 516-524.   DOI
13 Singh, K. K., Russell, J., Sigala, B., Zhang, Y., Williams, J. and Keshav, K. F. 1999. Mitochondrial DNA determines the cellular response to cancer therapeutic agents. Oncogene 18, 6641-6646.   DOI
14 Bralley, J. and Lord, R. 2001. Laboratory Evaluations in Molecular Medicine: Nutrients, Toxicants, and Cell Regulators, 175-208, Institute for Advances in Molecular Medicine: Norcross, GA, USA
15 Bell, E. L., Emerling, B. M., Ricoult, S. J. and Guarente, L. 2011. SirT3 suppresses hypoxia inducible factor 1alpha and tumor growth by inhibiting mitochondrial ROS production. Oncogene 30, 2986-2996.   DOI
16 Bohovych, I. and Khalimonchuk, O. 2016. Sending out an SOS: mitochondria as a signaling hub. Front. Cell. Dev. Biol. 4, 109.
17 Boland, M. L., Chourasia, A. H. and Macleod, K. F. 2013. Mitochondrial dysfunction in cancer. Front. Oncol. 3, 1-28.   DOI
18 Castro-Vega, L. J., Buffet, A., De Cubas, A. A., Cascon, A., Menara, M., Khalifa, E., Amar, L., Azriel, S., Bourdeau, I., Chabre, O., Curras-Freixes, M., Franco-Vidal, V., Guillaud- Bataille, M., Simian, C., Morin, A., Leton, R., Gomez-Grana, A., Pollard, P. J., Rustin, P., Robledo, M., Favier, J. and Gimenez-Roqueplo, A. P. 2014. Germline mutations in FH confer predisposition to malignant pheochromocytomas and paragangliomas. Hum. Mol. Genet. 23, 2440-2446.   DOI
19 Brookes, P. S., Yoon, Y., Robotham, J. L., Anders, M. W. and Sheu, S. S. 2004. Calcium, ATP, and ROS: a mitochondrial love-hate triangle. Am. J. Physiol. Cell. Physiol. 287, C817-833.   DOI
20 Butow, R. A. and Avadhani, N. G. 2004. Mitochondrial signaling: the retrograde response. Mol. Cell. 14, 1-15.   DOI
21 Hung, W. Y., Huang, K. H., Wu, C. W., Chi, C. W., Kao, H. L., Li, A. F., Yin, P. H. and Lee, H. C. 2012. Mitochondrial dysfunction promotes cell migration via reactive oxygen species-enhanced beta5-integrin expression in human gastric cancer SC-M1 cells. Biochim. Biophys. Acta. 1820, 1102-1110.   DOI
22 Hensen, E. F., Siemers, M. D., Jansen, J. C., Corssmit, E. P., Romijn, J. A., Tops, C. M., van der Mey, A. G., Devilee, P., Cornelisse, C. J., Bayley, J. P. and Vriends, A. H. 2011. Mutations in SDHD are the major determinants of the clinical characteristics of Dutch head and neck paraganglioma patients. Clin. Endocrinol. (Oxf). 75, 650-655.   DOI
23 Hirschey, M. D., Shimazu, T., Goetzman, E., Jing, E., Schwer, B., Lombard, D. B., Grueter, C. A., Harris, C., Biddinger, S., Ilkayeva, O. R., Stevens, R. D., Li, Y., Saha, A. K., Ruderman, N. B., Bain, J. R., Newgard, C. B., Farese, R. V., Jr., Alt, F. W., Kahn, C. R. and Verdin, E. 2010. SIRT3 regulates mitochondrial fatty-acid oxidation by reversible enzyme deacetylation. Nature 464, 121-125.   DOI
24 Hsu, C. C., Wu, L. C., Chi, C. W., Lee, H. C., Hsia, C. Y., Yin, P. H. and Yeh, T. S. 2015. Energy metabolism determines the sensitivity of human hepatocellular carcinoma cells to mitochondrial inhibitors and biguanide drugs. Oncol. Rep. 34, 1620-1628.   DOI
25 Hung, W. Y., Wu, C. W., Yin, P. H., Chang, C. J., Li, A. F., Chi, C. W., Wei, Y. H. and Lee, H. C. 2010. Somatic mutations in mitochondrial genome and their potential roles in the progression of human gastric cancer. Biochim. Biophys. Acta. 1800, 264-270.   DOI
26 Chandel, N. S., Maltepe, E., Goldwasser, E., Mathieu, C. E., Simon, M. C. and Schumacker, P. T. 1998. Mitochondrial reactive oxygen species trigger hypoxia-induced transcription. Proc. Natl. Acad. Sci. USA. 95, 11715-11720.   DOI
27 Wallace, D. C. 1994. Mitochondrial DNA sequence variation in human evolution and disease. Proc. Natl. Acad. Sci. USA. 91, 8739-8746.   DOI
28 Wallace, D. C. 2005. A mitochondrial paradigm of metabolic and degenerative diseases, aging, and cancer: a dawn for evolutionary medicine. Annu. Rev. Genet. 39, 359-407.   DOI
29 Chance, B., Sies, H. and Boveris, A. 1979. Hydroperoxide metabolism in mammalian organs. Physiol. Rev. 59, 527-605.   DOI
30 Chandel, N. S. 2015. Evolution of Mitochondria as Signaling Organelles. Cell. Metab. 22, 204-206.   DOI
31 Chang, C. J., Yin, P. H., Yang, D. M., Wang, C. H., Hung, W. Y., Chi, C. W., Wei, Y. H. and Lee, H. C. 2009. Mitochondrial dysfunction-induced amphiregulin upregulation mediates chemo-resistance and cell migration in HepG2 cells. Cell. Mol. Life. Sci. 66, 1755-1765.   DOI
32 Chatterjee, A., Mambo, E. and Sidransky, D. 2006. Mitochondrial DNA mutations in human cancer. Oncogene 25, 4663-4674.   DOI
33 Chitkara, D. K., Nurko, S., Shoffner, J. M., Buie, T. and Flores, A. 2003. Abnormalities in gastrointestinal motility are associated with diseases of oxidative phosphorylation in children. Am. J. Gastroenterol. 98, 871-877.   DOI
34 Liu, J., Killilea, D. W. and Ames, B. N. 2002. Age-associated mitochondrial oxidative decay: improvement of carnitine acetyltransferase substrate-binding affinity and activity in brain by feeding old rats acetyl-L- carnitine and/or R-alpha -lipoic acid. Proc. Natl. Acad. Sci. USA. 99, 1876-1881.   DOI
35 Liu, X., Kim, C. N., Yang, J., Jemmerson, R. and Wang, X. 1996. Induction of apoptotic program in cell-free extracts: requirement for dATP and cytochrome c. Cell 86, 147-157.   DOI
36 Lopez, J. and Tait, S. W. 2015. Mitochondrial apoptosis: killing cancer using the enemy within. Br. J. Cancer 112, 957-962.   DOI
37 Konradi, C., Eaton, M., MacDonald, M. L., Walsh, J., Benes, F. M. and Heckers, S. 2004. Molecular evidence for mitochondrial dysfunction in bipolar disorder. Arch. Gen. Psychiatry 61, 300-308.   DOI
38 Jazayeri, M., Andreyev, A., Will, Y., Ward, M., Anderson, C. M. and Clevenger, W. 2003. Inducible expression of a dominant negative DNA polymerase-gamma depletes mitochondrial DNA and produces a rho0 phenotype. J. Biol. Chem. 278, 9823-9830.   DOI
39 Kim, M. M., Clinger, J. D., Masayesva, B. G., Ha, P. K., Zahurak, M. L., Westra, W. H. and Califano, J. A. 2004. Mitochondrial DNA quantity increases with histopathologic grade in premalignant and malignant head and neck lesions. Clin. Cancer. Res. 10, 8512-8515.   DOI
40 Kim, S., Kim, D. H., Jung, W. H. and Koo, J. S. 2013. Succinate dehydrogenase expression in breast cancer. Springerplus 2, 299.   DOI
41 Launonen, V., Vierimaa, O., Kiuru, M., Isola, J., Roth, S., Pukkala, E., Sistonen, P., Herva, R. and Aaltonen, L. A. 2001. Inherited susceptibility to uterine leiomyomas and renal cell cancer. Proc. Natl. Acad. Sci. USA. 98, 3387-3392.   DOI
42 Lee, H. C., Chang, C. M. and Chi, C. W. 2010. Somatic mutations of mitochondrial DNA in aging and cancer progression. Aging. Res. Rev. 9, S47-S58.   DOI
43 Lee, H. C., Huang, K. H., Yeh, T. S. and Chi, C. W. 2014. Somatic alterations in mitochondrial DNA and mitochondrial dysfunction in gastric cancer progression. World. J. Gastroenterol. 20, 3950-3959.   DOI
44 Lee, H. C., Li, S. H., Lin, J. C., Wu, C. C., Yeh, D. C. and Wei, Y. H. 2004. Somatic mutations in the D-loop and decrease in the copy number of mitochondrial DNA in human hepatocellular carcinoma. Mutat. Res. 547, 71-78.   DOI
45 Lee, H. C., Yin, P. H., Lin, J. C., Wu, C. C., Chen, C. Y., Wu, C. W., Chi, C. W., Tam, T. N. and Wei, Y. H. 2005. Mitochondrial genome instability and mtDNA depletion in human cancers. Ann. N. Y. Acad. Sci. 1042, 109-122.   DOI
46 Wei, Y. H., Lu, C. Y., Lee, H. C., Pang, C. Y. and Ma, Y. S. 1998. Oxidative damage and mutation to mitochondrial DNA and age-dependent decline of mitochondrial respiratory function. Ann. N. Y. Acad. Sci. 854, 155-170.   DOI
47 Wallace, D. C., Fan, W. and Procaccio, V. 2010. Mitochondrial energetics and therapeutics. Annu. Rev. Pathol. 5, 297-348.   DOI
48 Wang, C. and Youle, R. J. 2009. The role of mitochondria in apoptosis. Annu. Rev. Genet. 43, 95-118.   DOI
49 Wang, Y., Liu, V. W., Xue, W. C., Cheung, A. N. and Ngan, H. Y. 2006. Association of decreased mitochondrial DNA content with ovarian cancer progression. Br. J. Cancer 95, 1087-1091.   DOI
50 Weinberg, S. E., Sena, L. A. and Chandel, N. S. 2015. Mitochondria in the regulation of innate and adaptive immunity. Immunity 42, 406-417.   DOI
51 Wiseman, A. and Attardi, G. 1978. Reversible tenfod reduction in mitochondria DNA content of human cells treated with ethidium bromide. Mol. Gen. Genet. 167, 51-63.   DOI
52 Wu, C. W., Yin, P. H., Hung, W. Y., Li, A. F., Li, S. H., Chi, C. W., Wei, Y. H. and Lee, H. C. 2005. Mitochondrial DNA mutations and mitochondrial DNA depletion in gastric cancer. Genes Chromosomes Cancer 44, 19-28.   DOI
53 Xiao, K., Jiang, J., Wang, W., Cao, S., Zhu, L., Zeng, H., Ouyang, R., Zhou, R. and Chen, P. 2013. Sirt3 is a tumor suppressor in lung adenocarcinoma cells. Oncol. Rep. 30, 1323-1328.   DOI
54 Maiese, K., Morhan, S. D. and Chong, Z. Z. 2007. Oxidative stress biology and cell injury during type 1 and type 2 diabetes mellitus. Curr. Neurovasc. Res. 4, 63-71.   DOI
55 Lu, J., Sharma, L. K. and Bai, Y. 2009. Implications of mitochondrial DNA mutations and mitochondrial dysfunction in tumorigenesis. Cell. Res. 19, 802-815.   DOI
56 Luft, R., Ikkos, D., Palmieri, G., Ernster, L. and Afzelius, B. 1962. A case of severe hypermetabolism of nonthyroid origin with a defect in the maintenance of mitochondrial respiratory control: a correlated clinical, biochemical, and morphological study. J. Clin. Invest. 41, 1776-1804.   DOI
57 Ma, Z. A., Zhao, Z. and Turk, J. 2012. Mitochondrial dysfunction and beta-cell failure in type 2 diabetes mellitus. Exp. Diabetes. Res. 2012, 703538.
58 Mambo, E., Chatterjee, A., Xing, M., Tallini, G., Haugen, B. R., Yeung, S. C., Sukumar, S. and Sidransky, D. 2005. Tumorspecific changes in mtDNA content in human cancer. Int. J. Cancer 116, 920-924.   DOI
59 Mansfield, K. D., Guzy, R. D., Pan, Y., Young, R. M., Cash, T. P., Schumacker, P. T. and Simon, M. C. 2005. Mitochondrial dysfunction resulting from loss of cytochrome c impairs cellular oxygen sensing and hypoxic HIF-alpha activation. Cell. Metab. 1, 393-399.   DOI
60 Cohen, B. H. and Gold, D. R. 2001. Mitochondrial cytopathy in adults: what we know so far. Cleve. Clin. J. Med. 68, 625-626, 629-642.   DOI
61 Contreras, L., Drago, I., Zampese, E. and Pozzan, T. 2010. Mitochondria: the calcium connection. Biochim. Biophys. Acta. 1797, 607-618.   DOI
62 Copeland, W. C. and Longley, M. J. 2003. DNA polymerase gamma in mitochondrial DNA replication and repair. ScientificWorldJournal 3, 34-44.   DOI
63 Karbowski, M. and Neutzner, A. 2012. Neurodegeneration as a consequence of failed mitochondrial maintenance. Acta. Neuropathol. 123, 157-171.   DOI
64 Jiang, W. W., Masayesva, B., Zahurak, M., Carvalho, A. L., Rosenbaum, E., Mambo, E., Zhou, S., Minhas, K., Benoit, N., Westra, W. H., Alberg, A., Sidransky, D., Koch, W. and Califano, J. 2005. Increased mitochondrial DNA content in saliva associated with head and neck cancer. Clin. Cancer Res. 11, 2486-2491.   DOI
65 Jo, A., Ham, S., Lee, G. H., Lee, Y. I., Kim, S., Lee, Y. S., Shin, J. H. and Lee, Y. 2015. Efficient Mitochondrial Genome Editing by CRISPR/Cas9. Biomed. Res. Int. 2015, 305716.
66 Kang, M. R., Kim, M. S., Oh, J. E., Kim, Y. R., Song, S. Y., Seo, S. I., Lee, J. Y., Yoo, N. J. and Lee, S. H. 2009. Mutational analysis of IDH1 codon 132 in glioblastomas and other common cancers. Int. J. Cancer 125, 353-355.   DOI
67 Kato, K., Radsak, K. D. and Koprowski, H. 1972. Differential effect of ethidium bromide and cytosine arabinoside on mitochondrial and nuclear DNA synthesis in HeLa cells. Z. Naturforsch. B. 27, 989-991.
68 Dan Dunn, J., Alvarez, L. A., Zhang, X. and Soldati, T. 2015. Reactive oxygen species and mitochondria: A nexus of cellular homeostasis. Redox. Biol. 6, 472-485.   DOI
69 Cordero, M. D., de Miguel, M., Carmona-Lopez, I., Bonal, P., Campa, F. and Maria Moreno-Fernandez, A. 2010. Oxidative stress and mitochondrial dysfunction in fibromyalgia. Neuro. Endocrinol. Lett. 31, 169-173.
70 Croteau, D. L. and Bohr, V. A. 1997. Repair of oxidative damage to nuclear and mitochondrial DNA in mammalian cells. J. Biol. Chem. 272, 25409-25412.   DOI
71 Degli Esposti, M. 2014. Bioenergetic evolution in proteobacteria and mitochondria. Genome Biol. Evol. 6, 3238-3251.   DOI
72 Desjardins, P., Frost, E. and Morais, R. 1985. Ethidium bromide- induced loss of mitochondrial DNA from primary chicken embryo fibroblasts. Mol. Cell. Biol. 5, 1163-1169.   DOI
73 Devine, M. J. and Kittler, J. T. 2018. Mitochondria at the neuronal presynapse in health and disease. Nat. Rev. Neurosci. 19, 63-80.   DOI
74 Diebold, L. and Chandel, N. S. 2016. Mitochondrial ROS regulation of proliferating cells. Free. Radic. Biol. Med. 100, 86-93.   DOI
75 Mao, P. and Reddy, P. H. 2010. Is multiple sclerosis a mitochondrial disease? Biochim. Biophys. Acta. 1802, 66-79.   DOI
76 Marin-Garcia, J. 2013. Methods to Study Mitochondrial Structure and Function, pp. 13-27, Springer US: Boston, MA, USA
77 Mayr, J. A., Meierhofer, D., Zimmermann, F., Feichtinger, R., Kogler, C., Ratschek, M., Schmeller, N., Sperl, W. and Kofler, B. 2008. Loss of complex I due to mitochondrial DNA mutations in renal oncocytoma. Clin. Cancer Res. 14, 2270-2275.   DOI
78 Lee, S. T., Wu, T. T., Yu, P. Y. and Chen, R. M. 2009. Apoptotic insults to human HepG2 cells induced by S-(+)-ketamine occurs through activation of a Bax-mitochondria- caspase protease pathway. Br. J. Anaesth. 102, 80-89.   DOI
79 Kawauchi, K., Araki, K., Tobiume, K. and Tanaka, N. 2008. p53 regulates glucose metabolism through an IKK-NF-${\kappa}B$ pathway and inhibits cell transformation. Nat. Cell. Biol. 10, 611-618.   DOI
80 Kim, H. S., Patel, K., Muldoon-Jacobs, K., Bisht, K. S., Aykin- Burns, N., Pennington, J. D., van der Meer, R., Nguyen, P., Savage, J., Owens, K. M., Vassilopoulos, A., Ozden, O., Park, S. H., Singh, K. K., Abdulkadir, S. A., Spitz, D. R., Deng, C. X. and Gius, D. 2010. SIRT3 is a mitochondria-localized tumor suppressor required for maintenance of mitochondrial integrity and metabolism during stress. Cancer Cell 17, 41-52.   DOI
81 Lee, W., Choi, H. I., Kim, M. J. and Park, S. Y. 2008. Depletion of mitochondrial DNA up-regulates the expression of MDR1 gene via an increase in mRNA stability. Exp. Mol. Med. 40, 109-117.   DOI
82 Li, C. H., Tzeng, S. L., Cheng, Y. W. and Kang, J. J. 2005. Chloramphenicol-induced mitochondrial stress increases p21 expression and prevents cell apoptosis through a p21- dependent pathway. J. Biol. Chem. 280, 26193-26199.   DOI
83 Li, J. M. and Shah, A. M. 2004. Endothelial cell superoxide generation: regulation and relevance for cardiovascular pathophysiology. Am. J. Physiol. Regul. Integr. Comp. Physiol. 287, R1014-1030.   DOI
84 Liemburg-Apers, D. C., Willems, P. H., Koopman, W. J. and Grefte, S. 2015. Interactions between mitochondrial reactive oxygen species and cellular glucose metabolism. Arch. Toxicol. 89, 1209-1226.   DOI
85 Limongelli, G., Masarone, D., D'Alessandro, R. and Elliott, P. M. 2012. Mitochondrial diseases and the heart: an overview of molecular basis, diagnosis, treatment and clinical course. Future. Cardiol. 8, 71-88.   DOI
86 Lin, C. S., Chang, S. C., Wang, L. S., Chou, T. Y., Hsu, W. H., Wu, Y. C. and Wei, Y. H. 2010. The role of mitochondrial DNA alterations in esophageal squamous cell carcinomas. J. Thorac. Cardiovasc. Surg. 139, 189-197 e184.   DOI
87 Naito, A., Carcel-Trullols, J., Xie, C. H., Evans, T. T., Mizumachi, T. and Higuchi, M. 2008. Induction of acquired resistance to antiestrogen by reversible mitochondrial DNA depletion in breast cancer cell line. Int. J. Cancer 122, 1506-1511.   DOI
88 Milligan, J. R., Aguilera, J. A. and Ward, J. F. 1993. Variation of single-strand break yield with scavenger concentration for the SV40 minichromosome irradiated in aqueous solution. Radiat. Res. 133, 158-162.   DOI
89 Miranda, S., Foncea, R., Guerrero, J. and Leighton, F. 1999. Oxidative stress and upregulation of mitochondrial biogenesis genes in mitochondrial DNA-depleted HeLa cells. Biochem. Biophys. Res. Commun. 258, 44-49.   DOI
90 Myhill, S., Booth, N. E. and McLaren-Howard, J. 2009. Chronic fatigue syndrome and mitochondrial dysfunction. Int. J. Clin. Exp. Med. 2, 1-16.
91 Naito, A., Cook, C. C., Mizumachi, T., Wang, M., Xie, C. H., Evans, T. T., Kelly, T. and Higuchi, M. 2008. Progressive tumor features accompany epithelial-mesenchymal transition induced in mitochondrial DNA-depleted cells. Cancer Sci. 99, 1584-1588.   DOI
92 Nass, M. M. 1970. Abnormal DNA patterns in animal mitochondria: ethidium bromide-induced breakdown of closed circular DNA and conditions leading to oligomer accumulation. Proc. Natl. Acad. Sci. USA. 67, 1926-1933.   DOI
93 Spadafora, D., Kozhukhar, N., Chouljenko, V. N., Kousoulas, K. G. and Alexeyev, M. F. 2016. Methods for efficient elimination of mitochondrial DNA from cultured cells. PLoS One 11, e0154684.   DOI
94 Lin, C. S., Lee, H. T., Lee, S. Y., Shen, Y. A., Wang, L. S., Chen, Y. J. and Wei, Y. H. 2012. High mitochondrial DNA copy number and bioenergetic function are associated with tumor invasion of esophageal squamous cell carcinoma cell lines. Int. J. Mol. Sci. 13, 11228-11246.   DOI
95 Du, X. L., Edelstein, D., Rossetti, L., Fantus, I. G., Goldberg, H., Ziyadeh, F., Wu, J. and Brownlee, M. 2000. Hyperglycemia- induced mitochondrial superoxide overproduction activates the hexosamine pathway and induces plasminogen activator inhibitor-1 expression by increasing Sp1 glycosylation. Proc. Natl. Acad. Sci. USA. 97, 12222-12226.   DOI
96 Duchen, M. R. 2004. Mitochondria in health and disease: perspectives on a new mitochondrial biology. Mol. Aspects. Med. 25, 365-451.   DOI
97 Sjoblom, T., Jones, S., Wood, L. D., Parsons, D. W., Lin, J., Barber, T. D., Mandelker, D., Leary, R. J., Ptak, J., Silliman, N., Szabo, S., Buckhaults, P., Farrell, C., Meeh, P., Markowitz, S. D., Willis, J., Dawson, D., Willson, J. K., Gazdar, A. F., Hartigan, J., Wu, L., Liu, C., Parmigiani, G., Park, B. H., Bachman, K. E., Papadopoulos, N., Vogelstein, B., Kinzler, K. W. and Velculescu, V. E. 2006. The consensus coding sequences of human breast and colorectal cancers. Science 314, 268-274.   DOI
98 Slonimski, P. P., Perrodin, G. and Croft, J. H. 1968. Ethidium bromide induced mutation of yeast mitochondria: complete transformation of cells into respiratory deficient non-chromosomal "petites". Biochem. Biophys. Res. Commun. 30, 232-239.   DOI
99 Son, G. and Han, J. 2018. Roles of mitochondria in neuronal development. BMB. Rep. 51, 549-556.   DOI
100 Sotgia, F., Martinez-Outschoorn, U. E. and Lisanti, M. P. 2011. Mitochondrial oxidative stress drives tumor progression and metastasis: should we use antioxidants as a key component of cancer treatment and prevention? BMC. Med. 9, 62.   DOI
101 Gabaldon, T. and Huynen, M. A. 2004. Shaping the mitochondrial proteome. Biochim. Biophys. Acta. 1659, 212-220.   DOI
102 Fernandez, D. and Perl, A. 2009. Metabolic control of T cell activation and death in SLE. Autoimmun. Rev. 8, 184-189.   DOI
103 Ferraresi, R., Troiano, L., Pinti, M., Roat, E., Lugli, E., Quaglino, D., Taverna, D., Bellizzi, D., Passarino, G. and Cossarizza, A. 2008. Resistance of mtDNA-depleted cells to apoptosis. Cytometry. A. 73, 528-537.
104 Finley, L. W., Carracedo, A., Lee, J., Souza, A., Egia, A., Zhang, J., Teruya-Feldstein, J., Moreira, P. I., Cardoso, S. M., Clish, C. B., Pandolfi, P. P. and Haigis, M. C. 2011. SIRT3 opposes reprogramming of cancer cell metabolism through HIF1alpha destabilization. Cancer Cell 19, 416-428.   DOI
105 Galluzzi, L., Kepp, O. and Kroemer, G. 2012. Mitochondria: master regulators of danger signalling. Nat. Rev. Mol. Cell. Biol. 13, 780-788.   DOI
106 Gammage, P. A., Moraes, C. T. and Minczuk, M. 2017. Mitochondrial genome engineering: The revolution may not be CRISPR-Ized. Trends Genet. 34, 101-110.   DOI
107 Gonzalez-Sanchez, E., Marin, J. J. G. and Perez, M. J. 2014. The expression of genes involved in hepatocellular carcinoma chemoresistance is affected by mitochondrial genome depletion. Mol. Pharm. 11, 1856-1868.   DOI
108 Nicolson, G. L. 2007. Metabolic syndrome and mitochondrial function: molecular replacement and antioxidant supplements to prevent membrane peroxidation and restore mitochondrial function. J. Cell. Biochem. 100, 1352-1369.   DOI
109 Nicolson, G. L. 2014. Mitochondrial dysfunction and chronic disease: treatment with natural supplements. Integr. Med. (Encinitas). 13, 35-43.
110 Spees, J. L., Olson, S. D., Whitney, M. J. and Prockop, D. J. 2006. Mitochondrial transfer between cells can rescue aerobic respiration. Proc. Natl. Acad. Sci. USA. 103, 1283-1288.   DOI
111 Starkov, A. A. 2008. The role of mitochondria in reactive oxygen species metabolism and signaling. Ann. N. Y. Acad. Sci. 1147, 37-52.   DOI
112 Swerdlow, R. H. 2011. Brain aging, Alzheimer's disease, and mitochondria. Biochim. Biophys. Acta. 1812, 1630-1639.   DOI
113 Pashkovskaia, N., Gey, U. and Rodel, G. 2018. Mitochondrial ROS direct the differentiation of murine pluripotent P19 cells. Stem. Cell. Res. 30, 180-191.   DOI
114 Owens, K. M., Aykin-Burns, N., Dayal, D., Coleman, M. C., Domann, F. E. and Spitz, D. R. 2012. Genomic instability induced by mutant succinate dehydrogenase subunit D (SDHD) is mediated by $O_2^{-\bullet}$ and $H_2O_2$. Free. Radic. Biol. Med. 52, 160-166.   DOI
115 Palmieri, L. and Persico, A. M. 2010. Mitochondrial dysfunction in autism spectrum disorders: cause or effect? Biochim. Biophys. Acta. 1797, 1130-1137.   DOI
116 Park, S. Y., Chang, I., Kim, J. Y., Kang, S. W., Park, S. H., Singh, K. and Lee, M. S. 2004. Resistance of mitochondrial DNA-depleted cells against cell death: role of mitochondrial superoxide dismutase. J. Biol. Chem. 279, 7512-7520.   DOI
117 Petros, J. A., Baumann, A. K., Ruiz-Pesini, E., Amin, M. B., Sun, C. Q., Hall, J., Lim, S., Issa, M. M., Flanders, W. D., Hosseini, S. H., Marshall, F. F. and Wallace, D. C. 2005. mtDNA mutations increase tumorigenicity in prostate cancer. Proc. Natl. Acad. Sci. USA. 102, 719-724.   DOI
118 Prince, J. A., Harro, J., Blennow, K., Gottfries, C. G. and Oreland, L. 2000. Putamen mitochondrial energy metabolism is highly correlated to emotional and intellectual impairment in schizophrenics. Neuropsychopharmacology 22, 284-292.   DOI
119 Tseng, L. M., Yin, P. H., Chi, C. W., Hsu, C. Y., Wu, C. W., Lee, L. M., Wei, Y. H. and Lee, H. C. 2006. Mitochondrial DNA mutations and mitochondrial DNA depletion in breast cancer. Genes Chromosomes Cancer 45, 629-638.   DOI
120 Tanaka, M., Kovalenko, S. A., Gong, J. S., Borgeld, H. J., Katsumata, K., Hayakawa, M., Yoneda, M. and Ozawa, T. 1996. Accumulation of deletions and point mutations in mitochondrial genome in degenerative diseases. Ann. N. Y. Acad. Sci. 786, 102-111.   DOI
121 Tzagoloff, A. 1982. Mitochondria, pp. 1-14, Springer US: New York, USA
122 Tzameli, I. 2012. The evolving role of mitochondria in metabolism. Trends. Endocrinol. Metab. 23, 417-419.   DOI
123 van der Wijst, M. G. P., van Tilburg, A. Y., Ruiters, M. H. J. and Rots, M. G. 2017. Experimental mitochondria-targeted DNA methylation identifies GpC methylation, not CpG methylation, as potential regulator of mitochondrial gene expression. Sci. Rep. 7, 177.   DOI
124 Zylber, E., Vesco, C. and Penman, S. 1969. Selective inhibition of the synthesis of mitochondria-associated RNA by ethidium bromide. J. Mol. Biol. 44, 195-204.   DOI
125 Yin, P. H., Lee, H. C., Chau, G. Y., Wu, Y. T., Li, S. H., Lui, W. Y., Wei, Y. H., Liu, T. Y. and Chi, C. W. 2004. Alteration of the copy number and deletion of mitochondrial DNA in human hepatocellular carcinoma. Br. J. Cancer. 90, 2390-2396.   DOI
126 Yu, M., Shi, Y., Wei, X., Yang, Y., Zhou, Y., Hao, X., Zhang, N. and Niu, R. 2007. Depletion of mitochondrial DNA by ethidium bromide treatment inhibits the proliferation and tumorigenesis of T47D human breast cancer cells. Toxicol. Lett. 170, 83-93.   DOI
127 Yu, M., Zhou, Y., Shi, Y., Ning, L., Yang, Y., Wei, X., Zhang, N., Hao, X. and Niu, R. 2007. Reduced mitochondrial DNA copy number is correlated with tumor progression and prognosis in Chinese breast cancer patients. IUBMB Life 59, 450-457.   DOI
128 Veltri, K. L., Espiritu, M. and Singh, G. 1990. Distinct genomic copy number in mitochondria of different mammalian organs. J. Cell. Physiol. 143, 160-164.   DOI
129 Gray, M. W. 1989. Origin and evolution of mitochondrial DNA. Annu. Rev. Cell. Biol. 5, 25-50.   DOI
130 van Waveren, C., Moraes, C. T., Sun, Y. and Cheung, H. S. 2006. Oxidative phosphorylation dysfunction modulates expression of extracellular matrix - Remodeling genes and invasion. Carcinogenesis 27, 409-418.   DOI
131 Victor, V. M., Apostolova, N., Herance, R., Hernandez- Mijares, A. and Rocha, M. 2009. Oxidative stress and mitochondrial dysfunction in atherosclerosis: mitochondriatargeted antioxidants as potential therapy. Curr. Med. Chem. 16, 4654-4667.   DOI
132 Vyas, S., Zaganjor, E. and Haigis, M. C. 2016. Mitochondria and cancer. Cell 166, 555-566.   DOI
133 Wallace, D. C. 2012. Mitochondria and cancer. Nat. Rev. Cancer 12, 685-698.   DOI
134 Guha, M. and Avadhani, N. G. 2013. Mitochondrial retrograde signaling at the crossroads of tumor bioenergetics, genetics and epigenetics. Mitochondrion 13, 577-591.   DOI
135 Graziewicz, M. A., Longley, M. J. and Copeland, W. C. 2006. DNA polymerase gamma in mitochondrial DNA replication and repair. Chem. Rev. 106, 383-405.   DOI
136 Green, D. R. and Reed, J. C. 1998. Mitochondria and apoptosis. Science 281, 1309-1312.   DOI
137 Green, K., Brand, M. D. and Murphy, M. P. 2004. Prevention of mitochondrial oxidative damage as a therapeutic strategy in diabetes. Diabetes 53 Suppl 1, S110-118.   DOI
138 Hallows, W. C., Yu, W., Smith, B. C., Devries, M. K., Ellinger, J. J., Someya, S., Shortreed, M. R., Prolla, T., Markley, J. L., Smith, L. M., Zhao, S., Guan, K. L. and Denu, J. M. 2011. Sirt3 promotes the urea cycle and fatty acid oxidation during dietary restriction. Mol. Cell. 41, 139-149.   DOI
139 Hamanaka, R. B. and Chandel, N. S. 2010. Mitochondrial reactive oxygen species regulate cellular signaling and dictate biological outcomes. Trends. Biochem. Sci. 35, 505-513.   DOI
140 Hanahan, D. and Weinberg, R. A. 2011. Hallmarks of Cancer: The Next Generation. Cell 144, 646-674.   DOI
141 Harper, M. E., Bevilacqua, L., Hagopian, K., Weindruch, R. and Ramsey, J. J. 2004. Ageing, oxidative stress, and mitochondrial uncoupling. Acta. Physiol. Scand. 182, 321-331.   DOI
142 Qiu, X., Brown, K., Hirschey, M. D., Verdin, E. and Chen, D. 2010. Calorie restriction reduces oxidative stress by SIRT3-mediated SOD2 activation. Cell. Metab. 12, 662-667.   DOI