Ca2+ transport and oxidative damage of mitochondria.
1. Mitochondria from a wide range of sources have the ability to accumulate Ca2+ down their electrochemical gradient mediated by a uniport mechanism. 2. Ca2+ efflux occurs via two separate pathways: a Na+/Ca2+ exchanger that predominates in mitochondria from excitable tissues and a Na(+)-independent pathway that predominates in mitochondria from non-excitable tissues. 3. The kinetic characteristics of these calcium influx-efflux pathways appear to be incompatible with any role for mitochondria as cytosolic Ca2+ buffers, under resting normal physiological conditions. Instead, the biological role of this Ca(2+)-transporting system seems to be the regulation of matrix Ca2+ in a range that permits the regulation of three intramitochondrial Ca(2+)-dependent dehydrogenases which catalyze rate-limiting reactions of the Krebs cycle. 4. Under conditions in which a high cytosolic Ca2+ concentration is sustained, the matrix Ca2+ concentration may attain levels that lead to impairment of mitochondrial functions such as inhibition of oxidative phosphorylation and increase in inner membrane permeability. 5. Accumulation of Ca2+ by mitochondria under conditions of oxidative stress induces an increase in inner membrane permeability by a mechanism that appears to be mediated by protein polymerization due to thiol cross-linking.
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Departamento de Bioquímica, Universidade Estadual de Campinas, SP, Brasil.
D000255:Adenosine Triphosphate / Q000096:biosynthesis; D000818:Animals; D017920:Antiporters / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D008564:Membrane Potentials / Q000502:physiology; D008928:Mitochondria / Q000378:metabolism*; D009243:NAD / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D019831:Sodium-Calcium Exchanger; D013438:Sulfhydryl Compounds / Q000378:metabolism
D017920:Antiporters; D017382:Reactive Oxygen Species; D019831:Sodium-Calcium Exchanger; D013438:Sulfhydryl Compounds; D009243:NAD; D000255:Adenosine Triphosphate; D002118:Calcium