Control of the pyridine nucleotide-linked Ca2+ release from mitochondria by respiratory substrates.
Oxidation of mitochondrial pyridine nucleotides followed by their hydrolysis promotes Ca2+ release from intact liver mitochondria. In most of the previous studies oxidation was achieved with pro-oxidants which were added to mitochondria respiring on succinate in the presence of rotenone, a site I-specific inhibitor of the respiratory chain. Here we investigate pro-oxidant dependent and independent Ca2+ release from mitochondria when respiration is supported either by the NAD(+)-linked substrate beta-hydroxybutyrate, or by succinate. In the presence, as well as in the absence, of the pro-oxidant t-butylhydroperoxide mitochondria retain Ca2+ much better with succinate than with beta-hydroxybutyrate as respiratory substrate. When Ca2+ release is induced by t-butylhydroperoxide succinate-supported Ca2+ retention is impeded by rotenone. Ca2+ release (pro-oxidant dependent or independent) is paralleled by oxidation and hydrolysis of intramitochondrial pyridine nucleotides, and Ca2+ retention is paralleled by reduction of pyridine nucleotides. It is concluded that the pyridine nucleotide-linked Ca2+ release from mitochondria can be controlled by respiratory substrates which regulate the intramitochondrial hydrolysis of oxidized pyridine nucleotides.
Gogvadze
V
V
Laboratory of Biochemistry I, Swiss Federal Institute of Technology (ETH), Zürich, Switzerland.
Schweizer
M
M
Richter
C
C
D020155:3-Hydroxybutyric Acid; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D016572:Cyclosporine / Q000494:pharmacology; D006868:Hydrolysis; D006885:Hydroxybutyrates / Q000494:pharmacology; D017136:Ion Transport / Q000187:drug effects / Q000502:physiology; D008930:Mitochondria, Liver / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D009250:NADP Transhydrogenases / Q000187:drug effects / Q000378:metabolism*; D010084:Oxidation-Reduction; D010545:Peroxides / Q000494:pharmacology; D051381:Rats; D017382:Reactive Oxygen Species; D012402:Rotenone / Q000494:pharmacology; D013386:Succinates / Q000494:pharmacology; D019802:Succinic Acid; D014475:Uncoupling Agents / Q000494:pharmacology; D020122:tert-Butylhydroperoxide
D006885:Hydroxybutyrates; D010545:Peroxides; D017382:Reactive Oxygen Species; D013386:Succinates; D014475:Uncoupling Agents; D012402:Rotenone; D016572:Cyclosporine; D020122:tert-Butylhydroperoxide; D019802:Succinic Acid; D009250:NADP Transhydrogenases; D002118:Calcium; D020155:3-Hydroxybutyric Acid