Dysfunction of rat liver mitochondria by selenite: induction of mitochondrial permeability transition through thiol-oxidation

• Published in: Biochemical and biophysical research communications 2002-06, Vol.294 (5), p.1130-1137
• Main Authors: Kim, Tae-soo, Jeong, Dae-won, Yun, Byung Yup, Kim, Ick Young
• Format: Article
• Language: English
• Subjects: Animals; Anticarcinogenic Agents - pharmacology; Apoptosis; Cytochrome c; Cytochrome c Group - metabolism; Dose-Response Relationship, Drug; Ion Channels - physiology; Membrane Potentials - drug effects; Mitochondria; Mitochondria, Liver - drug effects; Mitochondria, Liver - physiology; Mitochondrial membrane potential; Mitochondrial Membrane Transport Proteins; Mitochondrial Proteins - chemistry; Mitochondrial Proteins - metabolism; MPT, mitochondrial permeability transition; Oxidation-Reduction; Rats; Selenite; Sodium Selenite - pharmacology; Sulfhydryl Compounds - metabolism; Superoxides - metabolism; Thiol oxidation
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/S0006-291X(02)00612-5

Selenium is an essential trace element in mammals and is thought to play a chemopreventive role in human cancer, possibly by inducing tumor cell apoptosis. Mitochondria play a pivotal role in the induction of apoptosis in many cell types. The effects of selenite on mitochondrial function were therefore investigated. Selenite induced the oxidation and cross-linking of protein thiol groups, mitochondrial permeability transition (MPT), a decrease in the mitochondrial membrane potential, and the release of cytochrome c in mitochondria isolated from rat liver. Induction of the MPT by selenite was prevented by cyclosporin A, EGTA, or N-ethylmaleimide. These results thus indicate that selenite induces the MPT as a result of direct modification of protein thiol groups, resulting in the release of cytochrome c and a loss of mitochondrial membrane potential.