Response to the increase of oxidative stress and mutation of mitochondrial DNA in aging.
In the aging process, mitochondrial function gradually declines with an increase of mutations in mitochondrial DNA (mtDNA) in tissue cells. Some of the aging-associated mtDNA mutations have been shown to result in not only inefficient generation of ATP but also increased production of reactive oxygen species (ROS) such as superoxide anions (O2-) and hydrogen peroxide (H2O2) in the mitochondria of aging tissues. Extensive studies have revealed that such an increase of oxidative stress is a contributory factor for alterations in the expression and activities of antioxidant enzymes and increased oxidative damage to DNA, RNA, proteins, and lipids in tissues and cultured cells from elderly subjects. Recently, we observed that gene expression of several proteins and enzymes related to iron metabolism is altered and that aconitase is extremely susceptible to oxidative damage in senescent skin fibroblasts and in cybrids harboring aging-associated A8344G mutation of mtDNA. Of great importance is the perturbation at the protein and activity levels of several enzymes containing iron-sulfur clusters in skin fibroblasts of elderly subjects. Taken together, these findings suggest that cellular response to oxidative stress and oxidative damage elicited by mitochondrial dysfunction and/or mtDNA mutations plays an important role in human aging.
Ma
Yi-Shing
YS
Department of Biochemistry and Molecular Biology, School of Life Sciences, National Yang-Ming University, Taipei 112, Taiwan.
Wu
Shi-Bei
SB
Lee
Wan-Yu
WY
Cheng
Ju-San
JS
Wei
Yau-Huei
YH
D000154:Aconitate Hydratase / Q000378:metabolism; D000375:Aging / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D016922:Cellular Senescence / Q000235:genetics / Q000502:physiology; D004272:DNA, Mitochondrial / Q000235:genetics*; D006801:Humans; D007506:Iron-Sulfur Proteins / Q000378:metabolism; D008954:Models, Biological; D009154:Mutation; D018384:Oxidative Stress / Q000502:physiology*
D004272:DNA, Mitochondrial; D007506:Iron-Sulfur Proteins; D000154:Aconitate Hydratase