© 1997 Oxford University Press
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Mitochondria-Mediated Cell Injury1
*Department of Biochemistry and Molecular Biology, University of Minnesota Duluth, Minnesota 55812
Department of Pharmacology and Toxicology, Medical College of Wisconsin Milwaukee, Wisconsin 53226
Center for Neurosciences, University of Coimbra Coimbra, Portugal
§Department of Molecular Biosciences, University of California Davis, California 95616
¶Department of Biochemistry, Emory University School of Medicine Atlanta, Georgia 30322
Received April 11, 1997; accepted April 11, 1997
Mitochondria have long been known to participate in the process of cell injury associated with metabolic failure. Only recently, however, have we come to appreciate the role of mitochondria as primary intracellular targets in the initiation of cell dysfunction. In addition to ATP synthesis, mitochondria are also critical to modulation of cell redox status, osmotic regulation, pH control, and cytosolic calcium homeostasis and cell signaling. Mitochondria are susceptible to damage by oxidants, electrophiles, and lipophilic cations and weak acids. Chemical-induced mitochondrial dysfunction may be manifested as diverse bioenergetic disorders and considerable effort is required to distinguish between mechanisms involving critical mitochondrial targets and those in which mitochondrial dysfunction is secondary and plays only a modulatory role in cell injury. The following paragraphs review a few important examples of chemical-induced cytotoxic responses that are manifested as interference with mitochondrial metabolism and bioenergetics, gene regulation, or signal transduction in the form of apoptosis and altered cell cycle control. Greater understanding of the molecular mechanisms of mitochondrial bioenergetics, ion regulation, and genetics will lead to numerous additional examples of mitochondria-mediated cell injury, revealing important new insight regarding the prediction, prevention, diagnosis, and treatment of chemical-induced toxic tissue injury.