Mitochondria and Cancer

Gizel Gerdan; Şirin Kılıçturgay Yüksel; Cemaliye Boylu Akyerli

doi:10.17343/sdutfd.1562838

EN

Mitochondria and Cancer

Abstract

Mitochondria generate energy through cellular respiration and regulate various cellular processes such as heat production, generation and detoxification of reactive oxygen species, metabolism, apoptosis, and calcium homeostasis. In human cells, large numbers of mitochondria are present, each containing multiple copies of mitochondrial DNA. Variations in mitochondrial DNA have been associated with the onset and progression of various diseases, including neurological, cardiovascular, and metabolic disorders and also several cancers. These variants can be important drivers of cancer and may play a crucial role in tumor development. Additionally, mitochondrial copy number changes and structural variations, such as deletions can be associated with different types of cancer. Therefore, understanding the fundamental mechanisms is highly crucial. The molecular genetic correlations of mitochondrial DNA alterations and cancer, emphasize the importance of mitochondrial integrity in maintaining cellular homeostasis. Gaining knowledge of these associations can help us comprehend cancer processes as well as potential routes for targeted treatments and prevention, while further investigation is still required.

Keywords

Ethical Statement

The ethical approval is not required. This article does not contain any studies with human or animal subjects.

References

1. Hatefi Y. The mitochondrial electron transport and oxidative phosphorylation system. Annu Rev Biochem 1985;54:1015-69. doi: 10.1146/annurev.bi.54.070185.005055. PMID: 2862839.
2. Mitochondrion. In: Encyclopaedia Britannica. [Internet]. Chicago (IL): Encyclopaedia Britannica, Inc.; [cited 2024 Sep 21]. Available from: https://www.britannica.com/science/mitochondrion.
3. Frey TG, Mannella CA. The internal structure of mitochondria. Trends Biochem Sci 2000;25(7):319-24. doi: 10.1016/s0968-0004(00)01609-1. PMID: 10871882.
4. Collins TJ, Berridge MJ, Lipp P, Bootman MD. Mitochondria are morphologically and functionally heterogeneous within cells. EMBO J 2002;21(7):1616-27. doi: 10.1093/emboj/21.7.1616. PMID: 11927546; PMCID: PMC125942.
5. Kühlbrandt W. Structure and function of mitochondrial membrane protein complexes. BMC Biol 2015;13:89. doi: 10.1186/s12915-015-0201-x. PMID: 26515107; PMCID: PMC4625866.
6. Mitochondria in Health and Disease: Clinical Mitochondrial Medicine. Cambridge University Press; 2011.Viscomi C & Zeviani M. Available from: https://www.cambridge.org/us/universitypress/subjects/medicine/neurology-and-clinical-neuroscience/clinical-mitochondrial-medicine?format=PB&isbn=9780521132985
7. Cooper GM. The Cell: A Molecular Approach. 2nd ed. Sunderland (MA): Sinauer Associates; 2000. Chapter 14, Mitochondria.
8. Wallace DC. A mitochondrial paradigm of metabolic and degenerative diseases, aging, and cancer: a dawn for evolutionary medicine. Annu Rev Genet 2005;39:359-407. doi: 10.1146/annurev.genet.39.110304.095751. PMID: 16285865; PMCID: PMC2821041.

9. Wallace DC. Why do we still have a maternally inherited mitochondrial DNA? Insights from evolutionary medicine. Annu Rev Biochem 2007;76:781-821. doi: 10.1146/annurev.biochem.76.081205.150955. PMID: 17506638.
10. Mitchell P. Coupling of phosphorylation to electron and hydrogen transfer by a chemi-osmotic type of mechanism. Nature. 1961;191:144-8. doi: 10.1038/191144a0. PMID: 13771349.
11. Nelson D.L., Cox M.M. Lehninger Principles of Biochemistry. 7th Edition, W.H. Freeman, New York, 2017, 1328.
12. Wang C, Youle RJ. The role of mitochondria in apoptosis. Annu Rev Genet 2009;43:95-118. doi: 10.1146/annurev-genet-102108-134850. PMID: 19659442; PMCID: PMC4762029.
13. Boguszewska K, Szewczuk M, Kaźmierczak-Barańska J, Karwowski BT. The similarities between human mitochondria and bacteria in the context of structure, genome, and base excision repair system. Molecules 2020;25(12):2857. doi: 10.3390/molecules25122857. PMID: 32575813; PMCID: PMC7356350.
14. The Endosymbiotic Theory [Internet]. Community College of Baltimore Country (Cantonsville); 2023 [cited 2024 Sep 21]. Available from: https://bio.libretexts.org/@go/page/3220.
15. Nass Mm, Nass S. Intramitochondrial fibers with dna characteristics. I. fixation and electron staining reactions. J Cell Biol 1963;19(3):593-611. doi: 10.1083/jcb.19.3.593. PMID: 14086138; PMCID: PMC2106331.
16. Anderson S, Bankier AT, Barrell BG, de Bruijn MH et.al Sequence and organization of the human mitochondrial genome. Nature 1981;290(5806):457-65. doi: 10.1038/290457a0. PMID: 7219534.
17. Amorim A, Fernandes T, Taveira N. Mitochondrial DNA in human identification: A review. PeerJ 2019;7:e7314. doi: 10.7717/peerj.7314. PMID: 31428537; PMCID: PMC6697116.
18. Bandelt HJ, Kloss-Brandstätter A, Richards MB, Yao YG, et.al. The case for the continuing use of the revised Cambridge Reference Sequence (rCRS) and the standardization of notation in human mitochondrial DNA studies. J Hum Genet 2014;59(2):66-77. doi: 10.1038/jhg.2013.120. Epub 2013 Dec 5. PMID: 24304692.
19. MITOMAP: A Human Mitochondrial Genome Database [Internet]. MITOMAP Human MitoSeq; 2020 [cited 2024 Sep 21]. Available from: https://www.mitomap.org/MITOMAP/HumanMitoSeq.
20. Chen Z, Zhang F, Xu H. Human mitochondrial DNA diseases and Drosophila models. J Genet Genomics 2019;46(4):201-212. doi: 10.1016/j.jgg.2019.03.009. Epub 2019 Apr 23. PMID: 31076279.
21. Zhang C, Xue Y, Wang L, Wu Q, et.al. Progress on the physiological function of mitochondrial DNA and its specific detection and therapy. Chembiochem 2022;23(4):e202100474. doi: 10.1002/cbic.202100474. Epub 2021 Oct 27. PMID: 34661371.
22. Schon EA, DiMauro S, Hirano M. Human mitochondrial DNA: Roles of inherited and somatic mutations. Nat Rev Genet 2012;13(12):878-90. doi: 10.1038/nrg3275. PMID: 23154810; PMCID: PMC3959762.
23. van der Wijst MG, van Tilburg AY, Ruiters MH, Rots MG. Experimental mitochondria-targeted DNA methylation identifies GpC methylation, not CpG methylation, as potential regulator of mitochondrial gene expression. Sci Rep 2017;7(1):177. doi: 10.1038/s41598-017-00263-z. PMID: 28282966; PMCID: PMC5428053.
24. Calvo SE, Mootha VK. The mitochondrial proteome and human disease. Annu Rev Genomics Hum Genet 2010;11:25-44. doi: 10.1146/annurev-genom-082509-141720. PMID: 20690818; PMCID: PMC4397899.
25. Sharma H, Singh A, Sharma C, Jain SK, et.al. Mutations in the mitochondrial DNA D-loop region are frequent in cervical cancer. Cancer Cell Int 2005;5:34. doi: 10.1186/1475-2867-5-34. PMID: 16359547; PMCID: PMC1352382.
26. Tuppen HA, Blakely EL, Turnbull DM, Taylor RW. Mitochondrial DNA mutations and human disease. Biochim Biophys Acta 2010;1797(2):113-28. doi: 10.1016/j.bbabio.2009.09.005. Epub 2009 Sep 15. PMID: 19761752.
27. Alexeyev M, Shokolenko I, Wilson G, LeDoux S. The maintenance of mitochondrial DNA integrity--critical analysis and update. Cold Spring Harb Perspect Biol 2013;5(5):a012641. doi: 10.1101/cshperspect.a012641. PMID: 23637283; PMCID: PMC3632056.
28. Giles RE, Blanc H, Cann HM, Wallace DC. Maternal inheritance of human mitochondrial DNA. Proc Natl Acad Sci USA 1980;77(11):6715-9. doi: 10.1073/pnas.77.11.6715. PMID: 6256757; PMCID: PMC350359.
29. Harvey AJ. Mitochondria in early development: Linking the microenvironment, metabolism and the epigenome. Reproduction 2019;157(5):R159-R179. doi: 10.1530/REP-18-0431. PMID: 30870807.
30. Wang Y, Bogenhagen DF. Human mitochondrial DNA nucleoids are linked to protein folding machinery and metabolic enzymes at the mitochondrial inner membrane. J Biol Chem 2006;281(35):25791-802. doi: 10.1074/jbc.M604501200. Epub 2006 Jul 6. PMID: 16825194.
31. Stewart JB, Chinnery PF. The dynamics of mitochondrial DNA heteroplasmy: Implications for human health and disease. Nat Rev Genet 2015;16(9):530-42. doi: 10.1038/nrg3966. PMID: 26281784.
32. Smith ALM, Whitehall JC, Greaves LC. Mitochondrial DNA mutations in ageing and cancer. Mol Oncol 2022;16(18):3276-3294. doi: 10.1002/1878-0261.13291. Epub 2022 Jul 28. PMID: 35842901; PMCID: PMC9490137.
33. Wallace DC, Chalkia D. Mitochondrial DNA genetics and the heteroplasmy conundrum in evolution and disease. Cold Spring Harb Perspect Biol 2013;5(11):a021220. doi: 10.1101/cshperspect.a021220. PMID: 24186072; PMCID: PMC3809581.
34. Pérez-Amado CJ, Bazan-Cordoba A, Hidalgo-Miranda A, Jiménez-Morales S. Mitochondrial heteroplasmy shifting as a potential biomarker of cancer progression. Int J Mol Sci 2021;22(14):7369. doi: 10.3390/ijms22147369. PMID: 34298989; PMCID: PMC8304746.
35. Behnam B, Taghizadeh-Hesary F. Mitochondrial metabolism: A new dimension of personalized oncology. Cancers (Basel) 2023;15(16):4058. doi: 10.3390/cancers15164058. PMID: 37627086; PMCID: PMC10452105.
36. Parakatselaki ME, Ladoukakis ED. mtDNA heteroplasmy: Origin, detection, significance, and evolutionary consequences. Life (Basel) 2021;11(7):633. doi: 10.3390/life11070633. PMID: 34209862; PMCID: PMC8307225.
37. Sharma S, Verma K. Haplotype diversity of mitochondrial DNA in the Jat population of Haryana. 2023;9(4):320–30.
38. Stoneking M, Hedgecock D, Higuchi RG, Vigilant L, Erlich HA. Population variation of human mtDNA control region sequences detected by enzymatic amplification and sequence-specific oligonucleotide probes. Am J Hum Genet 1991;48(2):370-82. PMID: 1990843; PMCID: PMC1683035.
39. Stoneking M. Hypervariable sites in the mtDNA control region are mutational hotspots. Am J Hum Genet 2000;67(4):1029-32. doi: 10.1086/303092. Epub 2000 Aug 30. PMID: 10968778; PMCID: PMC1287875.
40. Lutz S, Weisser HJ, Heizmann J, Pollak S. A third hypervariable region in the human mitochondrial D-loop. Hum Genet 1997;101(3):384. PMID: 9439673.
41. Mitchell SL, Goodloe R, Brown-Gentry K, Pendergrass SA, et.al. Characterization of mitochondrial haplogroups in a large population-based sample from the United States. Hum Genet 2014;133(7):861-8. doi: 10.1007/s00439-014-1421-9. Epub 2014 Feb 1. PMID: 24488180; PMCID: PMC4113317.
42. Kenney MC, Chwa M, Atilano SR, Falatoonzadeh P, et.al Molecular and bioenergetic differences between cells with African versus European inherited mitochondrial DNA haplogroups: Implications for population susceptibility to diseases. Biochim Biophys Acta 2014;1842(2):208-19. doi: 10.1016/j.bbadis.2013.10.016. Epub 2013 Nov 4. PMID: 24200652; PMCID: PMC4326177.
43. Ferreira T, Rodriguez S. Mitochondrial DNA: Inherent complexities relevant to genetic analyses. Genes (Basel) 2024;15(5):617. doi: 10.3390/genes15050617. PMID: 38790246; PMCID: PMC11121663.
44. El-Hattab AW, Scaglia F. Mitochondrial cytopathies. Cell Calcium 2016;60(3):199-206. doi: 10.1016/j.ceca.2016.03.003. Epub 2016 Mar 4. PMID: 26996063.
45. Ryzhkova AI, Sazonova MA, Sinyov VV, Galitsyna EV, et.al. Mitochondrial diseases caused by mtDNA mutations: A mini-review. Ther Clin Risk Manag 2018;14:1933-1942. doi: 10.2147/TCRM.S154863. PMID: 30349272; PMCID: PMC6186303.
46. Alston CL, Rocha MC, Lax NZ, Turnbull DM, et.al. The genetics and pathology of mitochondrial disease. J Pathol 2017;241(2):236-250. doi: 10.1002/path.4809. Epub 2016 Nov 2. PMID: 27659608; PMCID: PMC5215404.
47. Gomes TMB, Ng YS, Pickett SJ, Turnbull DM, et.al. Mitochondrial DNA disorders: From pathogenic variants to preventing transmission. Hum Mol Genet 2021;30(R2):R245–R253. doi: 10.1093/hmg/ddab156.
48. DiMauro S. Mitochondrial encephalomyopathies--fifty years on: The Robert Wartenberg Lecture. Neurology 2013;81(3):281-91. doi: 10.1212/WNL.0b013e31829bfe89. PMID: 23858410; PMCID: PMC3959764.
49. Chinnery PF. Mitochondrial disease in adults: what's old and what's new? EMBO Mol Med 2015;7(12):1503-12. doi: 10.15252/emmm.201505079. PMID: 26612854; PMCID: PMC4693502.
50. Hong S, Kim S, Kim K, Lee H. Clinical approaches for mitochondrial diseases. Cells 2023;12(20):2494. doi: 10.3390/cells12202494. PMID: 37887337; PMCID: PMC10605124.
51. Taylor RW, Turnbull DM. Mitochondrial DNA mutations in human disease. Nat Rev Genet 2005;6(5):389-402. doi: 10.1038/nrg1606. PMID: 15861210; PMCID: PMC1762815.
52. Yang M, Xu L, Xu C, Cui Y, et.al. The mutations and clinical variability in maternally inherited diabetes and deafness: An analysis of 161 patients. Front Endocrinol (Lausanne) 2021;12:728043. doi: 10.3389/fendo.2021.728043. PMID: 34899594; PMCID: PMC8654930.
53. Yoshimi A, Ishikawa K, Niemeyer C, Grünert SC. Pearson syndrome: A multisystem mitochondrial disease with bone marrow failure. Orphanet J Rare Dis 2022;17(1):379. doi: 10.1186/s13023-022-02538-9. PMID: 36253820; PMCID: PMC9575259.
54. Ruhoy IS, Saneto RP. The genetics of Leigh syndrome and its implications for clinical practice and risk management. Appl Clin Genet 2014;7:221-34. doi: 10.2147/TACG.S46176. PMID: 25419155; PMCID: PMC4235479.
55. Stenton SL, Prokisch H. Genetics of mitochondrial diseases: Identifying mutations to help diagnosis. EBioMedicine 2020;56:102804.
56. Wang W, Zhao F, Ma X, Perry G, et.al Mitochondria dysfunction in the pathogenesis of Alzheimer's disease: recent advances. Mol Neurodegener 2020;15(1):30. doi: 10.1186/s13024-020-00376-6. PMID: 32471464; PMCID: PMC7257174.
57. Bhatia S, Rawal R, Sharma P, Singh T, et.al. Mitochondrial dysfunction in alzheimer's disease: Opportunities for drug development. Curr Neuropharmacol 2022;20(4):675-692. doi: 10.2174/1570159X19666210517114016. PMID: 33998995; PMCID: PMC9878959.
58. Visentin APV, Colombo R, Scotton E, Fracasso DS, et.al Targeting inflammatory-mitochondrial response in major depression: Current evidence and further challenges. Oxid Med Cell Longev 2020;2020:2972968. doi: 10.1155/2020/2972968. PMID: 32351669; PMCID: PMC7178465.
59. Bansal Y, Kuhad A. Mitochondrial dysfunction in depression. Curr Neuropharmacol 2016;14(6):610-8. doi: 10.2174/1570159x14666160229114755. PMID: 26923778; PMCID: PMC4981740.
60. Lee WE, Genetzakis E, Figtree GA. Novel strategies in the early detection and treatment of endothelial cell-specific mitochondrial dysfunction in coronary artery disease. Antioxidants (Basel) 2023;12(7):1359. doi: 10.3390/antiox12071359. PMID: 37507899; PMCID: PMC10376062.
61. Sinyov VV, Yureva A, Kuznetsova T, et al. Potential use of buccal epithelium for genetic diagnosis of atherosclerosis using mtDNA mutations. Vessel Plus 2017;1:145-150.
62. Wallace DC. Mitochondria and cancer. Nat Rev Cancer. 2012 Oct;12(10):685-98. doi: 10.1038/nrc3365. PMID: 23001348; PMCID: PMC4371788.
63. Larman TC, DePalma SR, Hadjipanayis AG; Cancer Genome Atlas Research Network; Protopopov A, Zhang J, et.al. Spectrum of somatic mitochondrial mutations in five cancers. Proc Natl Acad Sci USA 2012;109(35):14087-91. doi: 10.1073/pnas.1211502109. Epub 2012 Aug 13. PMID: 22891333; PMCID: PMC3435197.
64. Hertweck KL, Dasgupta S. The landscape of mtDNA modifications in cancer: A tale of two cities. Front Oncol 2017;7:262. doi: 10.3389/fonc.2017.00262. PMID: 29164061; PMCID: PMC5673620.
65. Alexandrov LB, Nik-Zainal S, Wedge DC, Aparicio SA, et.al. Signatures of mutational processes in human cancer. Nature 2013;500(7463):415-21. doi: 10.1038/nature12477. Epub 2013 Aug 14. Erratum in: Nature. 2013 Oct 10;502(7470):258. Imielinsk, Marcin [corrected to Imielinski, Marcin]. PMID: 23945592; PMCID: PMC3776390.
66. McMahon S, LaFramboise T. Mutational patterns in the breast cancer mitochondrial genome, with clinical correlates. Carcinogenesis 2014;35(5):1046-54. doi: 10.1093/carcin/bgu012. Epub 2014 Jan 18. PMID: 24442641; PMCID: PMC4004206.
67. Song Z, Laleve A, Vallières C, McGeehan JE, et.al. Human mitochondrial cytochrome b variants studied in yeast: Not all are silent polymorphisms. Hum Mutat 2016;37(9):933-41. doi: 10.1002/humu.23024. Epub 2016 Jun 27. PMID: 27291790; PMCID: PMC5094555.
68. Kloss-Brandstätter A, Weissensteiner H, Erhart G, Schäfer G, et.al. Validation of next-generation sequencing of entire mitochondrial genomes and the diversity of mitochondrial DNA mutations in oral squamous cell carcinoma. PLoS One 2015;10(8):e0135643. doi: 10.1371/journal.pone.0135643. PMID: 26262956; PMCID: PMC4532422.
69. Kurelac I, MacKay A, Lambros MB, Di Cesare E, et.al. Somatic complex I disruptive mitochondrial DNA mutations are modifiers of tumorigenesis that correlate with low genomic instability in pituitary adenomas. Hum Mol Genet 2013;22(2):226-38. doi: 10.1093/hmg/dds422. Epub 2012 Oct 9. PMID: 23049073.
70. Dasgupta S, Shao C, Keane TE, Duberow DP,et.al. Detection of mitochondrial deoxyribonucleic acid alterations in urine from urothelial cell carcinoma patients. Int J Cancer 2012;131(1):158-64. doi: 10.1002/ijc.26357. Epub 2011 Aug 30. PMID: 21826645; PMCID: PMC3328657.
71. Srinivasan S, Guha M, Kashina A, Avadhani NG. Mitochondrial dysfunction and mitochondrial dynamics-The cancer connection. Biochim Biophys Acta Bioenerg 2017;1858(8):602-614. doi: 10.1016/j.bbabio.2017.01.004. Epub 2017 Jan 16. PMID: 28104365; PMCID: PMC5487289.
72. Seyfried TN, Flores R, Poff AM, et.al. Metabolic therapy: A new paradigm for managing malignant brain cancer. Cancer Lett 2015;356(2 Pt A):289-300.
73. Stefano GB, Kream RM. Mitochondrial DNA heteroplasmy in human health and disease. Biomed Rep 2016;4(3):259-262.
74. Cavalcante GC, Ribeiro-Dos-Santos Â, de Araújo GS. Mitochondria in tumour progression: A network of mtDNA variants in different types of cancer. BMC Genom Data 2022;23(1):16. doi: 10.1186/s12863-022-01032-2. PMID: 35183124; PMCID: PMC8857862.
75. Canter JA, Kallianpur AR, Parl FF, Millikan RC. Mitochondrial DNA G10398A polymorphism and invasive breast cancer in African-American women. Cancer Res 2005;65(17):8028-33. doi: 10.1158/0008-5472.CAN-05-1428. PMID: 16140977.
76. Kopinski PK, Singh LN, Zhang S, Lott MT, et.al Mitochondrial DNA variation and cancer. Nat Rev Cancer 2021;21(7):431-445.
77. Liu VW, Wang Y, Yang HJ, Tsang PC, et.al Mitochondrial DNA variant 16189T>C is associated with susceptibility to endometrial cancer. Hum Mutat 2003;22(2):173-4. doi: 10.1002/humu.10244. PMID: 12872259.
78. Permuth-Wey J, Chen YA, Tsai YY, Chen Z, et.al. Inherited variants in mitochondrial biogenesis genes may influence epithelial ovarian cancer risk. Cancer Epidemiol Biomarkers Prev 2011;20(6):1131-45. doi: 10.1158/1055-9965.EPI-10-1224. Epub 2011 Mar 29. PMID: 21447778; PMCID: PMC3111851.
79. Shen L, Zhan X. Mitochondrial dysfunction pathway alterations offer potential biomarkers and therapeutic targets for ovarian cancer. Oxid Med Cell Longev 2022;2022:5634724. doi: 10.1155/2022/5634724. PMID: 35498135; PMCID: PMC9045977.
80. Lai MD, Xu J. Ribosomal proteins and colorectal cancer. Curr Genomics 2007;8(1):43-9. doi: 10.2174/138920207780076938. PMID: 18645623; PMCID: PMC2474683.
81. Bian M, Huang S, Yu D, Zhou Z. tRNA Metabolism and lung cancer: Beyond translation. Front Mol Biosci 2021;8:659388. doi: 10.3389/fmolb.2021.659388. PMID: 34660690; PMCID: PMC8516113.
82. Zhang J, Asin-Cayuela J, Fish J, Michikawa Y, et.al. Strikingly higher frequency in centenarians and twins of mtDNA mutation causing remodeling of replication origin in leukocytes. Proc Natl Acad Sci USA 2003;100(3):1116-21. doi: 10.1073/pnas.242719399. Epub 2003 Jan 21. PMID: 12538859; PMCID: PMC298736.
83. Chen K, Lu P, Beeraka NM, Sukocheva OA, et.al Mitochondrial mutations and mitoepigenetics: Focus on regulation of oxidative stress-induced responses in breast cancers. Semin Cancer Biol 2022;83:556-569. doi: 10.1016/j.semcancer.2020.09.012. Epub 2020 Oct 6. Erratum in: Semin Cancer Biol. 2022 Nov;86(Pt 2):1222. doi: 10.1016/j.semcancer.2022.07.002. PMID: 33035656.
84. Yuksel SK, Ozduman K, Yilmaz E, Pamir MN, et.al Analysis of mitochondrial DNA control region D-Loop in gliomas: Result of 52 patients. Turk Neurosurg 2021;31(3):368-372. doi: 10.5137/1019-5149.JTN.29805-20.2. PMID: 33759159.
85. Nicholls TJ, Minczuk M. In D-loop: 40 years of mitochondrial 7S DNA. Exp Gerontol 2014;56:175-81. doi: 10.1016/j.exger.2014.03.027. Epub 2014 Apr 4. PMID: 24709344.
86. Wagner A, Kosnacova H, Chovanec M, Jurkovicova D. Mitochondrial genetic and epigenetic regulations in cancer: Therapeutic potential. Int J Mol Sci 2022;23(14):7897. doi: 10.3390/ijms23147897. PMID: 35887244; PMCID: PMC9321253.
87. Lee HC, Yin PH, Lin JC, Wu CC, et.al. Mitochondrial genome instability and mtDNA depletion in human cancers. Ann N Y Acad Sci 2005;1042:109-22. doi: 10.1196/annals.1338.011. PMID: 15965052.
88. Kuo SJ, Chen M, Ma GC, Chen ST, et.al. Number of somatic mutations in the mitochondrial D-loop region indicates poor prognosis in breast cancer, independent of TP53 mutation. Cancer Genet Cytogenet 2010;201(2):94-101. doi: 10.1016/j.cancergencyto.2010.05.013. PMID: 20682393.
89. Stewart JB, Alaei-Mahabadi B, Sabarinathan R, Samuelsson T, et.al. Simultaneous DNA and RNA mapping of somatic mitochondrial mutations across diverse human cancers. PLoS Genet 2015;11(6):e1005333. doi: 10.1371/journal.pgen.1005333. PMID: 26125550; PMCID: PMC4488357.
90. Fliss MS, Usadel H, Caballero OL, Wu L, et.al. Facile detection of mitochondrial DNA mutations in tumors and bodily fluids. Science 2000;287(5460):2017-9. doi: 10.1126/science.287.5460.2017. PMID: 10720328.
91. Dasgupta S, Hoque MO, Upadhyay S, Sidransky D. Mitochondrial cytochrome B gene mutation promotes tumor growth in bladder cancer. Cancer Res 2008;68(3):700-6. doi: 10.1158/0008-5472.CAN-07-5532. PMID: 18245469.
92. Wallace DC, Shoffner JM, Trounce I, Brown MD, et.al. Mitochondrial DNA mutations in human degenerative diseases and aging. Biochim Biophys Acta 1995;1271(1):141-51. doi: 10.1016/0925-4439(95)00021-u. PMID: 7599200.
93. Filograna R, Mennuni M, Alsina D, Larsson NG. Mitochondrial DNA copy number in human disease: The more the better? FEBS Lett 2021;595(8):976-1002. doi: 10.1002/1873-3468.14021. Epub 2020 Dec 25. PMID: 33314045; PMCID: PMC8247411.
94. Guo J, Zheng L, Liu W, Wang X, et.al. Frequent truncating mutation of TFAM induces mitochondrial DNA depletion and apoptotic resistance in microsatellite-unstable colorectal cancer. Cancer Res 2011;71(8):2978-87. doi: 10.1158/0008-5472.CAN-10-3482. Epub 2011 Apr 5. PMID: 21467167; PMCID: PMC3710668.
95. Linkowska K, Jawień A, Marszałek A, Malyarchuk BA, et.al. Mitochondrial DNA Polymerase γ mutations and their implications in mtDNA alterations in colorectal cancer. Ann Hum Genet 2015;79(5):320-328. doi: 10.1111/ahg.12111. Epub 2015 Apr 7. PMID: 25850945.
96. Czegle I, Huang C, Soria PG, Purkiss DW, et.al. The Role of genetic mutations in mitochondrial-driven cancer growth in selected tumors: Breast and gynecological malignancies. Life (Basel) 2023;13(4):996. doi: 10.3390/life13040996. PMID: 37109525; PMCID: PMC10145875.
97. Russell OM, Gorman GS, Lightowlers RN, Turnbull DM. Mitochondrial diseases: Hope for the future. Cell 2020;181(1):168-188. doi: 10.1016/j.cell.2020.02.051. Epub 2020 Mar 26. PMID: 32220313.
98. Li Y, Sundquist K, Zhang N, Wang X, et.al. Mitochondrial related genome-wide Mendelian randomization identifies putatively causal genes for multiple cancer types. EBioMedicine 2023;88:104432. doi:10.1016/j.ebiom.2022.104432.
99. Metodiev MD, Spåhr H, Loguercio Polosa P, Meharg C, et.al. NSUN4 is a dual function mitochondrial protein required for both methylation of 12S rRNA and coordination of mitoribosomal assembly. PLoS Genet 2014;10(2):e1004110. doi: 10.1371/journal.pgen.1004110. PMID: 24516400; PMCID: PMC3916286.
100. Haney SL, Holstein SA. Targeting the Isoprenoid Biosynthetic Pathway in Multiple Myeloma. Int J Mol Sci. 2022 Dec 21;24(1):111. doi: 10.3390/ijms24010111. PMID: 36613550; PMCID: PMC9820492.
101. Liberti MV, Locasale JW. The warburg effect: How does it benefit cancer cells? Trends Biochem Sci 2016;41(3):211-218. doi: 10.1016/j.tibs.2015.12.001. Epub 2016 Jan 5. Erratum in: Trends Biochem Sci. 2016 Mar;41(3):287. Erratum in: Trends Biochem Sci. 2016 Mar;41(3):287. doi: 10.1016/j.tibs.2016.01.004. PMID: 26778478; PMCID: PMC4783224.
102. Wang Y, Patti GJ. The Warburg effect: A signature of mitochondrial overload. Trends Cell Biol 2023;33(12):1014-1020. doi: 10.1016/j.tcb.2023.03.013. Epub 2023 Apr 26. PMID: 37117116; PMCID: PMC10600323.
103. Liu Y, Sun Y, Guo Y, Shi X, et.al. An overview: The diversified role of mitochondria in cancer metabolism. Int J Biol Sci 2023;19(3):897-915. doi: 10.7150/ijbs.81609. PMID: 36778129; PMCID: PMC9910000.
104. Jose C, Bellance N, Rossignol R. Choosing between glycolysis and oxidative phosphorylation: A tumor's dilemma? Biochim Biophys Acta 2011;1807(6):552-61. doi: 10.1016/j.bbabio.2010.10.012. Epub 2010 Oct 16. PMID: 20955683.
105. Li J, Eu JQ, Kong LR, Wang L, et.al. Targeting metabolism in cancer cells and the tumour microenvironment for cancer therapy. Molecules 2020;25(20):4831. doi: 10.3390/molecules25204831. PMID: 33092283; PMCID: PMC7588013.
106. McCann E, O'Sullivan J, Marcone S. Targeting cancer-cell mitochondria and metabolism to improve radiotherapy response. Transl Oncol 2021;14(1):100905. doi: 10.1016/j.tranon.2020.100905. Epub 2020 Oct 14. PMID: 33069104; PMCID: PMC7562988.
107. Triggle CR, Mohammed I, Bshesh K, Marei I, et.al. Metformin: Is it a drug for all reasons and diseases? Metabolism 2022;133:155223. doi: 10.1016/j.metabol.2022.155223. Epub 2022 May 29. PMID: 35640743.
108. Guo Y, Hu B, Fu B, Zhu H. Atovaquone at clinically relevant concentration overcomes chemoresistance in ovarian cancer via inhibiting mitochondrial respiration. Pathol Res Pract 2021;224:153529. doi: 10.1016/j.prp.2021.153529. Epub 2021 Jun 19. PMID: 34174549.
109. Meng G, Li B, Chen A, Zheng M, et.al. Targeting aerobic glycolysis by dichloroacetate improves Newcastle disease virus-mediated viro-immunotherapy in hepatocellular carcinoma. Br J Cancer 2020;122(1):111-120. doi: 10.1038/s41416-019-0639-7. Epub 2019 Dec 10. PMID: 31819179; PMCID: PMC6964686.
110. Guo X, Yang N, Ji W, et.al. Mito-Bomb: Targeting mitochondria for cancer therapy. Adv Mater 2021;33(43):e2007778. doi: 10.1002/adma.202007778. Epub 2021 Sep 12. PMID: 34510563.
111. Cheng X, Feng D, Lv J, Cui X, et.al. Application prospects of triphenylphosphine-based mitochondria-targeted cancer therapy. Cancers (Basel) 2023;15(3):666. doi: 10.3390/cancers15030666. PMID: 36765624; PMCID: PMC9913854.
112. Bonekamp NA, Peter B, Hillen HS, Felser A, et.al. Small-molecule inhibitors of human mitochondrial DNA transcription. Nature 2020;588(7839):712-716. doi: 10.1038/s41586-020-03048-z. Epub 2020 Dec 16. PMID: 33328633.
113. Sun Y, Zhang H, Li Y, Wang X, et al. Mitochondria-targeted cancer therapy based on functional peptides. Chin Chem Lett 2023;34(5):107817.
114. Battogtokh G, Choi YS, Kang DS, Park SJ, et.al. Mitochondria-targeting drug conjugates for cytotoxic, anti-oxidizing and sensing purposes: current strategies and future perspectives. Acta Pharm Sin B 2018;8(6):862-880. doi: 10.1016/j.apsb.2018.05.006. Epub 2018 May 18. PMID: 30505656; PMCID: PMC6251809.
115. De Francesco EM, Ózsvári B, Sotgia F, Lisanti MP. Dodecyl-TPP targets mitochondria and potently eradicates cancer stem cells (CSCs): Synergy with FDA-approved drugs and natural compounds (Vitamin C and Berberine). Front Oncol 2019;9:615. doi: 10.3389/fonc.2019.00615. PMID: 31440463; PMCID: PMC6692486.
116. Hennrich U, Kopka K. The first FDA- and EMA-approved radiopharmaceutical for peptide receptor radionuclide therapy. Pharmaceuticals (Basel) 2019;12(3):114. doi: 10.3390/ph12030114. PMID: 31362406; PMCID: PMC6789871.
117. Poczta A, Rogalska A, Marczak A. Treatment of multiple myeloma and the role of melphalan in the era of modern therapies-current research and clinical approaches. J Clin Med 2021;10(9):1841. doi: 10.3390/jcm10091841. PMID: 33922721; PMCID: PMC8123041.
118. Jung HS, Lee JH, Kim K, et.al. A Mitochondria-targeted cryptocyanine-based photothermogenic photosensitizer. J Am Chem Soc 2017;139(29):9972-9978. doi: 10.1021/jacs.7b04263. Epub 2017 Jul 11. PMID: 28644025; PMCID: PMC5807084.
119. Wang Q, Xu J, Geng R, et.al. High performance one-for-all phototheranostics: NIR-II fluorescence imaging guided mitochondria-targeting phototherapy with a single-dose injection and 808 nm laser irradiation. Biomaterials 2020;231:119671. doi: 10.1016/j.biomaterials.2019.119671. Epub 2019 Dec 5. PMID: 31855624.
120. Libretexts. 12.4: The Citric Acid Cycle and Electron Transport. Chemistry LibreTexts [Internet]. 2020 Dec 17 [cited 2024 Sep 21]. Available from: https://chem.libretexts.org/Courses/Saint_Marys_College_Notre_Dame_IN/CHEM_118_(Under_Construction)/CHEM_118_Textbook/12%3A_Metabolism_(Biological_Energy)/12.4%3A_The_Citric_Acid_Cycle_and_Electron_Transport
121. Koklesova L, Mazurakova A, Samec M, Kudela E, et.al. Mitochondrial health quality control: Measurements and interpretation in the framework of predictive, preventive, and personalized medicine. EPMA J 2022;13(2):177-193. doi: 10.1007/s13167-022-00281-6. PMID: 35578648; PMCID: PMC9096339.
122. Cold Spring Harbor Laboratory's DNA Learning Center. Mitochondrial DNA [Internet]. Cold Spring Harbor (NY): Cold Spring Harbor Laboratory; c2023 [cited 2024 Sep 23]. Available from: https://dnalc.cshl.edu/view/16001-Mitochondrial-DNA.html
123. Errichiello E, Venesio T. Mitochondrial DNA variations in tumors: Drivers or passengers? 2018. doi:10.5772/intechopen.75188.

Details

Primary Language

English

Subjects

Cancer Genetics, Cancer Cell Biology

Journal Section

Review

Authors

Gizel Gerdan
0009-0001-5886-3269
Türkiye

Şirin Kılıçturgay Yüksel
0000-0002-7130-2933
Türkiye

Cemaliye Boylu Akyerli ^*
0000-0002-7263-2969
Türkiye

Early Pub Date

February 19, 2025

Publication Date

March 27, 2025

Submission Date

October 7, 2024

Acceptance Date

December 23, 2024

Published in Issue

Year 2025 Volume: 32 Number: 1

DOI

https://doi.org/10.17343/sdutfd.1562838

IZ

https://izlik.org/JA37XZ69WP

Cite

RIS / Bibtex

APA

Gerdan, G., Kılıçturgay Yüksel, Ş., & Boylu Akyerli, C. (2025). Mitochondria and Cancer. Medical Journal of Süleyman Demirel University, 32(1), 95-106. https://doi.org/10.17343/sdutfd.1562838

AMA

1.Gerdan G, Kılıçturgay Yüksel Ş, Boylu Akyerli C. Mitochondria and Cancer. Med J SDU. 2025;32(1):95-106. doi:10.17343/sdutfd.1562838

Chicago

Gerdan, Gizel, Şirin Kılıçturgay Yüksel, and Cemaliye Boylu Akyerli. 2025. “Mitochondria and Cancer”. Medical Journal of Süleyman Demirel University 32 (1): 95-106. https://doi.org/10.17343/sdutfd.1562838.

EndNote

Gerdan G, Kılıçturgay Yüksel Ş, Boylu Akyerli C (March 1, 2025) Mitochondria and Cancer. Medical Journal of Süleyman Demirel University 32 1 95–106.

IEEE

[1]G. Gerdan, Ş. Kılıçturgay Yüksel, and C. Boylu Akyerli, “Mitochondria and Cancer”, Med J SDU, vol. 32, no. 1, pp. 95–106, Mar. 2025, doi: 10.17343/sdutfd.1562838.

ISNAD

Gerdan, Gizel - Kılıçturgay Yüksel, Şirin - Boylu Akyerli, Cemaliye. “Mitochondria and Cancer”. Medical Journal of Süleyman Demirel University 32/1 (March 1, 2025): 95-106. https://doi.org/10.17343/sdutfd.1562838.

JAMA

1.Gerdan G, Kılıçturgay Yüksel Ş, Boylu Akyerli C. Mitochondria and Cancer. Med J SDU. 2025;32:95–106.

MLA

Gerdan, Gizel, et al. “Mitochondria and Cancer”. Medical Journal of Süleyman Demirel University, vol. 32, no. 1, Mar. 2025, pp. 95-106, doi:10.17343/sdutfd.1562838.

Vancouver

1.Gizel Gerdan, Şirin Kılıçturgay Yüksel, Cemaliye Boylu Akyerli. Mitochondria and Cancer. Med J SDU. 2025 Mar. 1;32(1):95-106. doi:10.17343/sdutfd.1562838