Prooxidant-induced Ca2+ release from liver mitochondria. Specific versus nonspecific pathways.
Ca2+ release from mitochondria can be induced by a variety of chemically different prooxidants. Release induced by these compounds is possibly regulated by protein mono(ADP)ribosylation, and leaves mitochondria initially intact. Excessive "cycling" (continuous release and uptake) of Ca2+ by mitochondria leads to their damage, as shown by a decreased membrane potential, fast Ca2+ release, and impairment of ATP synthesis. When cycling is prevented by Ca2+ chelators or by inhibition of the uptake route with ruthenium red, prooxidants still induce Ca2+ release but mitochondria remain intact. It has recently been suggested that formation of a "pore" in the inner mitochondrial membrane participates in the Ca2+ release mechanism. We find that the prooxidant-induced Ca2+ release is not paralleled by sucrose entry into, or K+ release from, or swelling of mitochondria, provided Ca2+ cycling is prevented. Thus, the prooxidant-induced Ca2+ release does not require formation of a "pore." We conclude that the release occurs via a specific pathway.
Richter
C
C
Laboratory of Biochemistry I, Swiss Federal Institute of Technology (ETH), Zürich.
Schlegel
J
J
Schweizer
M
M
D000818:Animals; D001692:Biological Transport; D002118:Calcium / Q000378:metabolism*; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008564:Membrane Potentials; D008930:Mitochondria, Liver / Q000378:metabolism*; D008933:Mitochondrial Swelling; D010084:Oxidation-Reduction; D010545:Peroxides / Q000494:pharmacology; D051381:Rats; D013481:Superoxides / Q000494:pharmacology; D014812:Vitamin K / Q000494:pharmacology; D020122:tert-Butylhydroperoxide
D010545:Peroxides; D013481:Superoxides; D014812:Vitamin K; D020122:tert-Butylhydroperoxide; D006861:Hydrogen Peroxide; D002118:Calcium