Mitochondrial DNA mutation

Conditions caused by mutations in mitochondrial DNA often involve multiple organ systems. The effects of these conditions are most pronounced in organs and tissues that require a lot of energy (such as the heart, brain, and muscles). Although the health consequences of inherited mitochondrial DNA mutations vary widely, frequently observed features include muscle weakness and wasting, problems with movement, diabetes, kidney failure, heart disease, loss of intellectual functions (dementia), hearing loss, and abnormalities involving the eyes and vision. 

Wallace DC, Singh G, Lott MT, et al. Mitochondrial DNA mutation associated with Leber s hereditary optic neuropathy. Science 1988 242(4884) 1427-1430. 

There are at least three ways in which mitochondrial ATP generation can be impaired mutations in mitochondrial DNA, mutations in nuclear DNA and effects of toxic compounds. The reactions in mitochondrial metabolism that are affected by some toxic compounds are described in Appendix 9.12. 

Proliferation Inhibitor of DNA polymerase-gamma (e.g., nucleoside reverse transcriptase inhibitors) inhibition of mitochondrial protein synthesis (e.g., oxazolidinone antibiotics) mitochondrial DNA mutation (e.g.. oxidative injury by ethanol)... 

Jiang, Y., Hall, T. A., Hofstadler, S. A., and Naviaux, R. K. (2007). Mitochondrial DNA mutation detection by electrospray mass spectrometry. Clin. Chem. 53 195-203. 

MITOCHONDRIAL DNA MUTATIONS AND OXIDATIVE STRESS IN MITOCHONDRIAL DISEASES... 

Ml. Ma, Y. S., Studies of the response to oxidative stress of the cybrids harboring the A8344G mitochondrial DNA mutation. Master s thesis. Institute of Biochemistry, National Yang-Ming University, Taipei, Taiwan, 1997. 

M13. Mirabella, M., Di Giovanni, S., Silvestri, G., Tonali, P., and Servidei, S., Apoptosis in mitochondrial encephalomyopathies with mitochondrial DNA mutations A potential pathogenic mechanism. Brain 123, 93-104 (2000). 

Z3. Zeviani, M., Mariotti, C., Antozzi, C., Fratta, G. M., Rustin, P., and Prelle, A., OXPHOS defects and mitochondrial DNA mutations in mitochondrial myopathy. Muscle Nerve (Suppl. 3), SI 70-S174 (1995). 

Shoffner JM, Wallace DC Oxidative phosphorylation diseases and mitochondrial DNA mutations diagnosis and treatment. Annu Rev Nutr 14 535-568,1994. 

Taylor RW, Turnbull DM. Mitochondrial DNA mutations in human disease. Nat. Rev. Genet. 2005 6 389 02. 

Hutchin T. Sensorineural hearing loss and the 1555G mitochondrial DNA mutation. Acta Otolaryngol 1999 119(l) 48-52. 

Parfait B, Rustin P, Munnich A, Rotig A. Coamplification of nuclear pseudogenes and assessment of heteroplasmy of mitochondrial DNA mutations. Biochem Biophys Res Commun 1998 247 57-9. 

Andreu AL, Marti R, Hirano M. Analysis of human mitochondrial DNA mutations. Metliods Molec Biol 2003 217 185-97. 

Schon EA, Bonilla E, DiMauro S. Mitochondrial DNA mutations and pathogenesis. J Bioener Biomemb 1997 29 131-49. 

Lagouge M, Larsson NG (2013) The role of mitochondrial DNA mutations and free radicals in disease and ageing. J Intern Med 273 529-543... 

TABLE 14-7 Correlations Found between Mitochondrial DNA Mutations and Human Diseases ... 

The bioenergetic defects resulting from mtDNA mutations may be a common cause of degenerative diseases (Table 14-7). Defects in nuclear-cytoplasmic interaction are generally the resultant of autosomal dominant mutations complex disease states result from depletion of mtDNAs from tissues. Mitochondrial DNA mutations are associated with a broad spectrum of chronic degenerative diseases with a variety of clinical presentations. Identical mutations are associated with very different phenotypes and the same phenotype can be associated with different mutations. 

Soong NW, Hinton DR, Gortopassi G, Amheim N. 1992. Mosaicism for a specific somatic mitochondrial DNA mutation in adult human brain. Nat Genet 2 318-323. 

Linnane A,Marzuki S, Ozawa T, Tanaka M (1989) Mitochondrial DNA mutations as an important contributor to ageing and degenerative diseases. Lancet 8639 642-645... 

Abu-Amero KK, Alzahrani AS, Zou M, Shi Y. High frequency of somatic mitochondrial DNA mutations in human thyroid carcinomas and complex 1 respiratory defect in thyroid cancer cell lines. Oncogene. 2005 24 1455-1460. 

Beckman, K. B. and Ames, B. N. Endogenous oxidative damage of mitochondrial DNA. Mutation Research 424 51-58 1999. 

Wallace, D.C. (1989) Mitochondrial DNA mutations and neuromuscular diseases. Trends Genet. 5 9-14. 

LeDoux SP, Driggers WJ, Hollensworth BS, Wilson GL (1999) Repair of alkylation and oxidative damage in mitochondrial DNA. Mutation Res 434 149-159 Leist M, Single B, Castoldi AF, Kiihnle S, Nicotera P (1997) Intracellular adenosine triphosphate (ATP) concentration a switch in the decision between apoptosis and necrosis. J Exp Med 185 1481-1486... 

Martin AM, Hammond E, Nolan D, Pace C, Boer MD, Taylra- L, Moore H, Martinez OP, Christiansen FT, Mallal S (2003) Accumulation of mitochondrial DNA mutations in hiunan immunodeficiency virus-infected patients treated with nucleoside-analogue reverse transcriptase inhibitors. Am J Hum Genet 72 549-560... 

---