The role of mitochondria in ageing and carcinogenesis.
Mitochondria can perform multiple cellular functions including energy production, cell proliferation and apoptosis. These organelles contain their own genetic material, mitochondrial DNA (mtDNA), which is maternally inherited. Although much smaller than the nuclear genome, mtDNA is equally important, as it has been hypothesized to play a crucial role in ageing and carcinogenesis. This is partly due to the fact that mitochondria represent the major site for the generation of cellular oxidative stress and play a key role in mediating programmed cell death (apoptosis). Damage to mtDNA is therefore an important contributor to human ageing, cancer and neurodegenerative diseases. The most relevant footprints of mtDNA damage are point mutations of single bases, or deletions of the 16.5-kb mitochondrial genome. This review will focus on the key roles of mitochondrial function and mtDNA in oxidative stress production and as a mediator of apoptosis, and on the use of mtDNA as a biomarker of sun exposure. This will be related to the contribution of mitochondria and mtDNA in the ageing process and cancer, with a specific focus on human skin. In conclusion, it is likely that the interplay between nuclear and mitochondrial genes may hold the final understanding of the mitochondrial role in these disease processes.
Birch-Machin
M A
MA
Dermatological Sciences, School of Clinical and Laboratory Sciences, University of Newcastle upon Tyne, Newcastle upon Tyne, UK. m.a.birch-machin@newcastle.ac.uk
D000375:Aging / Q000378:metabolism*; D017209:Apoptosis / Q000502:physiology; D004249:DNA Damage; D004272:DNA, Mitochondrial / Q000235:genetics / Q000502:physiology* / Q000528:radiation effects; D050259:Genes, Mitochondrial / Q000502:physiology; D006801:Humans; D009369:Neoplasms / Q000209:etiology; D018384:Oxidative Stress / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D014466:Ultraviolet Rays
D004272:DNA, Mitochondrial; D017382:Reactive Oxygen Species