Role of mitochondria in toxic oxidative stress.
Oxidative stress and mitochondrial oxidative damage have been implicated in the etiology of numerous common diseases. The critical mitochondrial events responsible for oxidative stress-mediated cell death (toxic oxidative stress), however, have yet to be defined. Several oxidative events implicated in toxic oxidative stress include alterations in mitochondrial lipids (e.g., cardiolipin), mitochondrial DNA, and mitochondrial proteins (eg. aconitase and uncoupling protein 2). Furthermore, recent findings indicate the enrichment of mitochondrial membranes with vitamin E protects cells against the toxic effects of oxidative stress. This review briefly summarizes the role of these mitochondrial events in toxic oxidative stress, including: 1) the protective role of mitochondrial vitamin E in toxic oxidative stress, 2) the role of mitochondrial DNA in toxic oxidative stress, 3) the interaction between cardiolipin and cytochrome c in mitochondrial regulation of apoptosis, 4) the role of mitochondrial aconitase in oxidative neurodegeneration, and 5) the role of mitochondrial uncoupling protein 2 in the pathogenesis of type 2 diabetes.
Fariss
Marc W
MW
Department of Pharmaceutical Sciences, University of Colorado Cancer Center, Denver, CO 80262, USA. marc.fariss@uchsc.edu
Chan
Catherine B
CB
Patel
Manisha
M
Van Houten
Bennett
B
Orrenius
Sten
S
D000154:Aconitate Hydratase / Q000378:metabolism; D000818:Animals; D016923:Cell Death; D045304:Cytochromes c / Q000378:metabolism; D004272:DNA, Mitochondrial / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008928:Mitochondria / Q000187:drug effects*; D024101:Mitochondrial Proteins; D018384:Oxidative Stress; D010100:Oxygen / Q000378:metabolism; D010766:Phosphorylation; D017382:Reactive Oxygen Species; D014810:Vitamin E / Q000378:metabolism
D004272:DNA, Mitochondrial; D024101:Mitochondrial Proteins; D017382:Reactive Oxygen Species; D014810:Vitamin E; D045304:Cytochromes c; D000154:Aconitate Hydratase; D010100:Oxygen