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Molecular Interventions 5:94-111, (2005)
© American Society for Pharmacology and Experimental Therapeutics
10.1124/mi.5.2.7
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Review

ROLE of MITOCHONDRIA in TOXIC OXIDATIVE STRESS

Marc W. Fariss1,2, Catherine B. Chan3, Manisha Patel1,4, Bennett Van Houten5 and Sten Orrenius6

1 Department of Pharmaceutical Sciences, 2 University of Colorado Cancer Center, University of Colorado Health Sciences Center, Denver, CO 80262, USA;
3 Department of Biomedical Sciences, University of Prince Edward Island, Charlottetown, PE Canada C1A 4P3;
4 Program in Neuroscience, University of Colorado Health Sciences Center, Denver, CO 80262, USA;
5 Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA;
6 Institute of Environmental Medicine, Division of Toxicology, Karolinska Institutet, SE-171 77 Stockholm, Sweden


{Fariss_ta}

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.




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