CONTROL OF THE PYRIDINE NUCLEOTIDE-LINKED CA2+ RELEASE FROM MITOCHONDRIA BY RESPIRATORY SUBSTRATES

Oxidation of mitochondrial pyridine nucleotides followed by their hydr olysis promotes Ca2+ release from intact liver mitochondria. In most o f the previous studies oxidation was achieved with pro-oxidants which were added to mitochondria respiring on succinate in the presence of r otenone, a site I-specific inhibitor of the respiratory chain. Here we investigate pro-oxidant dependent and independent Ca2+ release from m itochondria when respiration is supported either by the NAD(+)-linked substrate beta-hydroxybutyrate, or by succinate. In the presence, as w ell as in the absence, of the pro-oxidant t-butylhydroperoxide mitocho ndria retain Ca2+ much better with succinate than with beta-hydroxybut yrate as respiratory substrate. When Ca2+ release is induced by t-buty lhydroperoxide succinate-supported Ca2+ retention is impeded by roteno ne. 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 nucleotide s. It is concluded that the pyridine nucleotide-linked Ca2+ release fr om mitochondria can be controlled by respiratory substrates which regu late the intramitochondrial hydrolysis of oxidized pyridine nucleotide s.