The Relevance of Mitochondrial DNA Mutation in Human Diseases and Forensic Sciences: Review Article

Authors

  • Ruaa Hussein Ali Forensic DNA Center for Research and Training, Al-Nahrain University, Jadiriya, Baghdad, Iraq
  • Farhan Khaleel Hussein Department of Biology, College of Education for Pure Sciences, Kirkuk University, Kirkuk, Iraq
  • Dmoaa Majid Nasar College of Pharmacy, Thi-Qar University, Iraq
  • Asmaa Abd Al salam Salem College of Applied Science, University of Fallujah, Fallujah, Iraq

DOI:

https://doi.org/10.22401/

Keywords:

Forensic sciences , Human diseases , Mitochondrial DNA , diseases , MtDNA mutations

Abstract

Several studies have been carried out on mitochondrial DNA mutation in human diseases. Mitochondria are self-contained organelles with their DNA. The primary function of mitochondria is oxidative phosphorylation (OXPHOS), which is how the Electron Transport Chain (ETC) provides energy to the cell. Reactive oxygen species (ROS), which can oxidative destroy DNA, proteins, and macromolecules like lipids, are one of the process's potentially hazardous byproducts. Compared to mitochondrial DNA (mtDNA), nuclear DNA is better protective and has more repair mechanisms, making it more susceptible to oxidative damage that might result in mutations. This review focuses on the illnesses caused by mtDNA mutations known as "mitochondrial diseases. Numerous characteristics of (mtDNA), mainly those related to matrilineal heredity, a high duplicate number, and the absence of recombination, are advantageous for forensic study. Old bones, teeth, and hair are used as forensic samples for analysis, along with other biological samples with low levels of DNA. Different mtDNA haplogroups can affect longevity and risk of infection, in addition to being used to determine a person's geographic origin.

References

[1] Amorim, A.; Fernandes, T.; Taveira, N.; "Mitochondrial DNA in human identification" : a review. Peer J., 7: 1-24, 2019.

[2] Dong, X. C.; Liu, C.; Zhuo, G. C.; Ding, Y.; "Potential Roles of mtDNA mutations in PCOS-IR" : a review’’. Diabetes Metab Syndr Obes.,16: 139-149, 2023.

[3] Glancy, B.; Kim, Y.; Katti, P.; Willingham, T. B.; "The functional impact of mitochondrial structure across subcellular scales". Front. physiol., 11: 1-24,2020.

[4] Vadakedath, S.; Kandi, V.; Jayashankar, C. A.; Vijayan, S.; Achyut, K. C.; Uppuluri, S.; Kumar J. r, P. P.;" Mitochondrial Deoxyribonucleic Acid (mtDNA), Maternal Inheritance, and Their Role in the Development of Cancers": A Scoping Review. Cureus J., 15(6):1-7, 2023.

[5] Xian, H.; Liou, Y. C.; "Functions of outer mitochondrial membrane proteins: mediating the crosstalk between mitochondrial dynamics and mitophagy". Cell Death Differ., 28(3): 827-842, 2021.

[6] Fromenty, B.; "Alteration of mitochondrial DNA homeostasis in drug-induced liver injury". Food Chem Toxicol., 135: 1-49, 2020. ‏

[7] Al–Zubaidi, M. M.; Mahdi, A. A. L.; Al-Tabra, R. H.; Al-Sammaraie, H. K. I.; Abd el_Jabbar, B. A.; Jawad, A. A.; Hameed, S. N.; "Mitochondrial DNA in Fornescis: Principles, Applications, and Limitations". Al-Nahrain J. Sci., 27(2):50-62,2024.

[8] Fourdrilis, S.; de Frias Martins, A. M.; Backeljau, T.; "Relation between mitochondrial DNA hyperdiversity, mutation rate and mitochondrial genome evolution in Melarhaphe neritoides (Gastropoda: Littorinidae) and other Caenogastropoda" . Sci. Rep., 8(1): 1-12,‏ 2018.

[9] Wang, L.; Cheng, H. X.; Zhou, Y. H.; Ma, M.; "Clinical significance of the D-loop gene mutation in mitochondrial DNA in laryngeal cancer".Onco Targets ther.,14: 3461-3466, 2021.

[10] ‏Peng, S.; Gao, J.; Stojkov, D.; Yousefi, S.; Simon, H. U.; "Established and emerging roles for mitochondria in neutrophils". Immunol. Rev., 314(1): 413-426,2023.

[11] Dahal, S.; Raghavan, S. C.; "Mitochondrial genome stability in human: understanding the role of DNA repair pathways". Biochem.J., 478(6): 1179-1197,2021.

[12] Begriche, K.; Penhoat, C.; Bernabeu-Gentey, P.; Massart, J.; Fromenty, B.; "Acetaminophen-Induced Hepatotoxicity in Obesity and Nonalcoholic Fatty Liver Disease" : J. Crit. Rev., 3(1): 33-53,2023.‏

[13] Louvet, A.; Ntandja Wandji, L. C.; Lemaître, E.; Khaldi, M.; Lafforgue, C.; Artru, F.; Mathurin, P.; "Acute liver injury with therapeutic doses of acetaminophen": a prospective study. Hepatol., 73(5): 1945-1955,2021.

[14] Nguyen, N. T.; Umbaugh, D. S.; Sanchez-Guerrero, G.; Ramachandran, A.; Jaeschke, H.; "Kupffer cells regulate liver recovery through induction of chemokine receptor CXCR2 on hepatocytes after acetaminophen overdose in mice". Arch. Toxicol.,96:305-320 ,2022.

[15] Ramachandran, A.;Jaeschke, H.; "Mitochondria in Acetaminophen-Induced Liver Injury and Recovery": A Concise Review. Livers J., 3(2): 219-231, 2023.

[16] Yapa, N. M.; Lisnyak, V.; Reljic, B.; Ryan, M. T.; "Mitochondrial dynamics in health and disease". FEBS letters, 595(8): 1184-1204, 2021.‏

[17] Sato, K.; "Multiple roles of endocytosis and autophagy in intracellular remodeling during oocyte-to-embryo transition". Pro. Japan Acad., Series B, 98(5): 207-221,2022.

[18] Duan, M.; Chen, L.; Ge, Q.; Lu, N.; Li, J.; Pan, X.; Lu, Z.; "Evaluating heteroplasmic variations of the mitochondrial genome from whole genome sequencing data". Gene J., 699: 145-154,2019.

[19] Lin, Y.; Yang, B.; Huang, Y.; Zhang, Y.; Jiang, Y.;Ma, L.; Shen,Y.Q.; "Mitochondrial DNA-targeted therapy": A novel approach to combat cancer. Cell Insight, 100113,2023.

[20] Li, H.; Slone, J.; Fei, L.;Huang, T.; "Mitochondrial DNA variants and common diseases: a mathematical model for the diversity of age-related mtDNA mutations" . Cells J., 8(6): 608,2019.

[21] Kozakiewicz, P.; Grzybowska-Szatkowska, L.; Ciesielka, M.; Rzymowska, J.; "The role of mitochondria in carcinogenesis". Int. J. Mol. Sci., 22(10): 5100, 2021.

[22] Luo, S.; Valencia, C. A.; Zhang, J.; Lee, N. C.; Slone, J.; Gui, B.; Huang, T.; "Biparental inheritance of mitochondrial DNA in humans". Pro. National Acad. Sci., 115(51): 13039-13044,‏2018.

[23] Tang, Z.; Lu, Z.; Chen, B.; Zhang, W.; Chang, H. Y.; Hu, Z.; Xu, J.; "A genetic bottleneck of mitochondrial DNA during human lymphocyte development". Mol. Biol. Evol., 39(5):1-12,2022.

[24] Massart, J.; Begriche, K.; Hartman, J. H.; "Fromenty, B. "Role of mitochondrial cytochrome P450 2E1 in healthy and diseased liver". Cells J., 11(2): 288,2022. ‏

[25] Vazquez, J. H.; Clemens, M. M.; Allard, F. D.; Yee, E. U.; Kennon-McGill, S.; Mackintosh, S. G.;McGill, M. R.;"Identification of serum biomarkers to distinguish hazardous and benign aminotransferase elevations. Toxicol. Sci., 173(2): 244-254, 2020. ‏

[26] Hussein, M. A.; Abdulridha, R. H.; Sodani, I. J.; Al-Ward, M. A.; Jaafar, M. R.; Al-Sammarrie, H. K. I.; Safir, N. H.; "Mitochondrial DNA and Disease: Areview”. Al-Nahrain J. Sci., 27(2): 81-90, 2024.

[27] Jaberi, E.; Tresse, E.; Grønbæk, K.; Weischenfeldt, J.; Issazadeh-Navikas, S.; "Identification of unique and shared mitochondrial DNA mutations in neurodegeneration and cancer by single-cell mitochondrial DNA structural variation sequencing (MitoSV-seq)". EBioMedicine, 57 : 1-17, 2020. ‏

[28] Zapico, S. C.; Ubelaker, D. H.; "mtDNA mutations and their role in aging, diseases and forensic sciences". Aging dis., 4(6): 364,‏ 2013.

[29] Ramachandran, A.; Umbaugh, D. S.; Jaeschke, H.; "Mitochondrial dynamics in drug-induced liver injury". Livers, 1(3): 102-115, 2021.

[30] Ahmed, Q. A.; Almubarak, B. M. M.; Salih ,A.A.; "The effect of oxidative stress on the kidneys. Biol. Pharm .Sci., 28(2): 215-219, 2024.

[31] Miyazono, Y.; Hirashima, S.; Ishihara, N.; Kusukawa, J.; Nakamura, K. I.; Ohta, K.; "Uncoupled mitochondria quickly shorten along their long axis to form indented spheroids, instead of rings, in a fission-independent manner".Sci. Rep., 8(1): 350, 2018.

[32] Nemani, N.; Carvalho, E.; Tomar, D.; Dong, Z.; Ketschek, A.; Breves, S. L.; Madesh, M.; "MIRO-1 determines mitochondrial shape transition upon GPCR activation and Ca2+ stress" .Cell Rep., 23(4): 1005-1019, 2018.

[33] Umbaugh, D. S.; Nguyen, N. T.; Jaeschke, H.; Ramachandran, A.; "Mitochondrial membrane potential drives early change in mitochondrial morphology after acetaminophen exposure". Toxicol. Sci., 180(1): 186-195, 2021. ‏

[34] Du, K.; Ramachandran, A.; Weemhoff, J. L.; Woolbright, B. L.; Jaeschke, A. H.; Chao, X.; Jaeschke, H.; "Mito-tempo protects against acute liver injury but induces limited secondary apoptosis during the late phase of acetaminophen hepatotoxicity". Arch. Toxicol., 93: 163-178,‏2019.

[35] Connell, J. R.; Benton, M. C.; Lea, R. A.; Sutherland, H. G.; Haupt, L. M.; Wright, K. M.; Griffiths, L. R.; "Evaluating the suitability of current mitochondrial DNA interpretation guidelines for multigenerational whole mitochondrial genome comparisons". J. Fore. Sci., 67(5): 1766-1775, 2022. ‏

[36] Taylor, R. W.; Turnbull, D. M.; "Mitochondrial DNA mutations in human disease". Nat. Revi. Gene., 6(5): 389-402, 2005. ‏‏

[37] Palodhi, A.; Ghosh, S.; Biswas, N. K.; Basu, A.; Majumder, P. P.; Maitra, A.; "Profiling of genomic alterations of mitochondrial DNA in gingivobuccal oral squamous cell carcinoma: Implications for disease progress". Mitochondrion, 46: 361-369, 2019. ‏

[38] Shu, H. Y.; Li, H. C.; Xie, W. Q.; Ni, B., Zhou, H. Y.; "Cell carcinoma". Biomed. Rep., 10(1): 23-28,‏ 2019.

[39] Russell, O. M.; Gorman, G. S.; Lightowlers, R. N.; Turnbull, D. M.; "Mitochondrial diseases" : hope for the future. Cell J., 181(1): 168-188, 2020.

[40] Sultana, G. N. N.; Sultan, M. Z.; "Mitochondrial DNA and methods for forensic identification". J. Fore. Sci. Crimin, Inves, 9(1):1-5, 2018.

[41] Sukser, V.; Rokić, F.; Barbarić, L.; Korolija, M.; "Assessment of Illumina® Human mtDNA Genome assay: workflow evaluation with development of analysis and interpretation guidelines". Int. J. Leg. Med., 135(4): 1161-1178, 2021.

[42] Gammage, P. A.; Viscomi, C.; Simard, M. L.; Costa, A. S.; Gaude, E.; Powell, C. A.; "Minczuk, M.; Genome editing in mitochondria corrects a pathogenic mtDNA mutation in vivo". Nat. Med., 24(11): 1691-1695,2018. ‏

[43] Cihlar, J. C.; Amory, C.; Lagacé, R.; Roth, C.; Parson, W.; Budowle, B.; "Developmental validation of a MPS workflow with a PCR-based short amplicon whole mitochondrial genome panel". Genes J., 11(11): 1-31,‏ 2020. ‏

[44] Holt, C. L.; Stephens, K. M.; Walichiewicz, P.; Fleming, K. D.; Forouzmand, E.; Wu, S. F.; "Human mitochondrial control region and mtgenome: design and forensic validation of NGS multiplexes, sequencing and analytical software". Genes J., 12(4): 599, 2021. ‏ ‏

[45] Basu Ball, W.; Neff, J. K.; Gohil, V. M.; "The role of nonbilayer phospholipids in mitochondrial structure and function". FEBS letters, 592(8): 1273-1290, 2018. ‏ ‏

[46] Cuenca, D.; Battaglia, J.; Halsing, M.; Sheehan, S.; "Mitochondrial sequencing of missing persons DNA casework by implementing Thermo Fisher’s precision ID mtDNA whole genome assay". Genes J., 11(11):1-17, 2020. ‏‏

[47] Annis, S.; Fleischmann, Z.; Khrapko, M.; Franco, M.; Wasko, K.; Woods, D.; Khrapko, K.; "Quasi-Mendelian paternal inheritance of mitochondrial DNA: A notorious artifact, or anticipated behavior" Pro. National Acad. Sci., 116(30): 14797-14798,‏ 2019. ‏

[48] Lutz-Bonengel, S.; Parson, W.; "No further evidence for paternal leakage of mitochondrial DNA in humans yet". Pro. National Acad. Sci., 116(6): 1821-1822, 2019. ‏ ‏

[49] Salas, A.; Schönherr, S.; Bandelt, H. J.; Gómez-Carballa, A.; Weissensteiner, H.; "Extraordinary claims require extraordinary evidence in the case of asserted mtDNA biparental inheritance". bioRxiv, 47: 1-10, 2019.

[50] Wei, W.; Pagnamenta, A. T.; Gleadall, N.; Sanchis-Juan, A., Stephens, J., Broxholme, J.; Chinnery, P. F.; "Nuclear-mitochondrial DNA segments resemble paternally inherited mitochondrial DNA in humans". Nat. Comm., 11(1): 1-11,2020. ‏

[51] Huber, N.; Parson, W.; Dür, A.; "Next generation database search algorithm for forensic mitogenome analyses". Forensic Science Int. Gene., 37: 204-214,2018. ‏ ‏

[52] Williams, S. B.; Ye, Y.; Huang, M.; Chang, D. W.; Kamat, A. M.; Pu, X.; Wu, X.; "Mitochondrial DNA content as risk factor for bladder cancer and its association with mitochondrial DNA polymorphisms". Cancer Prev. Res., 8(7): 607-613,2015. ‏

[53] Gorden, E. M.; Sturk-Andreaggi, K.; Marshall, C.; "Repair of DNA damage caused by cytosine deamination in mitochondrial DNA of forensic case samples". Fore. Sci. Inter Genet., 34: 257-264,‏ 2018.

[54] Loreille, O.; Ratnayake, S.; Bazinet, A. L.; Stockwell, T. B.; Sommer, D. D.; Rohland, N.; Irwin, J. A.; "Biological sexing of a 4000-year-old Egyptian mummy head to assess the potential of nuclear DNA recovery from the most damaged and limited forensic specimens". Genes J., 9(3): 135,2018. ‏

[55] Bruijns, B.; Tiggelaar, R.; Gardeniers, H.; "Massively parallel sequencing techniques for forensics": A review. Electrophoresis J., 39(21): 2642-2654,2018.

[56] Churchill, J. D.; Stoljarova, M.; King, J. L.; Budowle, B.; "Massively parallel sequencing-enabled mixture analysis of mitochondrial DNA samples". Int. J. leg. Med., 132: 1263-1272, 2018. ‏

[57] Strobl, C.; Eduardoff, M.; Bus, M. M.; Allen, M.; Parson, W.; "Evaluation of the precision ID whole MtDNA genome panel for forensic analyses". Fore. Sci. Int. Gene., 35: 21-25, 2018.

[58] ‏Woerner, A. E.; Ambers, A.; Wendt, F. R.; King, J. L., Moura-Neto, R. S., Silva, R., & Budowle, B.; "Evaluation of the precision ID mtDNA whole genome panel on two massively parallel sequencing systems". Fore.Sci. Int Gene., 36: 213-224, 2018. ‏

[59] Cai, S.; Zhao, M.; Zhou, B.; Yoshii, A.; Bugg, D.; Villet, O.; Tian, R.; "Mitochondrial dysfunction in macrophages promotes inflammation and suppresses repair after myocardial infarction". J. Clin. Investi., 133(4):1-14,2023. ‏

[60] Young, B.; King, J. L.; Budowle, B., Armogida, L.; "A technique for setting analytical thresholds in massively parallel sequencing-based forensic DNA analysis". PLoS One, 12(5): 1-15, 2017. ‏

[61] Poletto, M. M.; Malaghini, M.; Silva, J. S.; Bicalho, M. G.; Braun-Prado, K.; "Mitochondrial DNA control region diversity in a population from Parana state—increasing the Brazilian forensic database". Int. J. Leg. Med., 133: 347-351,‏ 2019.

Downloads

Published

2025-03-15

Issue

Section

Articles

How to Cite

(1)
The Relevance of Mitochondrial DNA Mutation in Human Diseases and Forensic Sciences: Review Article. ANJS 2025, 28 (1), 96-106. https://doi.org/10.22401/.