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. Author manuscript; available in PMC: 2020 Feb 1.
Published in final edited form as: Biochim Biophys Acta Mol Basis Dis. 2018 Nov 9;1865(2):285–297. doi: 10.1016/j.bbadis.2018.09.035

Table 2.

Changes in mtDNA and mitochondrial function are summarized in the age-related diseases discussed in section 8.

mtDNA in Age-Related Diseases
Disease Rodent / Cell Culture Humans

Parkinson’s disease • Complex I inhibitors induce parkinsonian symptoms in rodents [142, 143] • Reduced complex I activity [144]
• mtDNA deletions in the striatum [145] and substantia niagra [146] significantly higher in Parkinson’s disease than aging alone.
• mtDNA polymerase PolG mutations [148]
• G11778A mtDNA mutation, which impairs complex I, has been reported to cause Parkinson’s disease [147].
Alzheimer’s disease • Mitochondrial dysfunction in APP mice [151]
• Mutation of mtDNA proof reading accelerates amyloid pathology [218].
• mtDNA deletions produce mitochondrial dysfunction but do not alter Aβ plaque formation [219].
• Complex IV dysfunction [149, 150]
• Increased mtDNA mutations [152]
• Increased mtDNA in cytoplasm [153]
• Increased mtDNA oxidative damage [154, 220]
• No difference in mtDNA damage between healthy elderly patients and elderly patients with AD [155]
• H5 haplogroup enriched in AD patients [157]
Sarcopenia • Mitochondrial abnormalities and mtDNA deletions correlate with age-related muscle loss [158].
• Clonal expansion of mtDNA deletions occur in muscles with age [158].
• Fibers deficient in complex IV activity increase with age and possess mtDNA deletions [159].
• mtDNA deletions accumulate in muscle with age, eventually accounting for >90% of total mtDNA [161].
Heart failure • Cardiac specific deletion of DNase II causes mortality, myocarditis and cardiomyopathy under heart pressure overload [168].
• Depletion of mtDNA nucleoid proteins causes mtDNA escape to the cytosol, triggering proinflammatory response [169].
• The mtDNA A3243G mutation leads to cardiomyopathy [163].
• OPA1, involved in mitochondrial fusion dynamics, is diminished in heart disease patients and OPA1 mutations are linked with a decline in mtDNA and age-related cardiac dysfunction [164].
• Increased circulating extracellular mtDNA in patients with coronary heart disease [165, 166].
Diabetes • High glucose increases mtDNA damage [171].
• Transfer of mtDNA from a mouse tumor into mouse embryonic cells predisposed mice to diabetes, lymphoma and metastasis [178].
• Elevated mtDNA damage [170]
• Lower mtDNA copy number [177]
• Increased circulating extracellular mtDNA in patients with diabetes [167]
• Mutation at mtDNA position 3243 is linked with diabetes and deafness [172, 173].
• Mutation at mtDNA position 3316 increases diabetes risk [174].
• Large mtDNA deletions associated with familial diabetes [175, 176].
Cancer • mtDNA mutations reported in esophageal, endometrial [181, 182], colorectal [183], prostate [221], breast [222], ovarian [223], gastric [224], hepatocellular [225], pancreatic [226] and lung cancers [227] as well as several others (reviewed in [228])