Evidence that adrenaline activates key oxidative enzymes in rat liver by increasing intramitochondrial [Ca2+]

Abstract

The effects of intramitochondrial Ca2+ on the activities of the Ca2+-sensitive intramitochondrial enzymes, (i) pyruvate dehydrogenase (PDH) phosphate phosphatase, and (ii) oxoglutarate dehydrogenase (OGDH), were investigated in intact rat liver mitochondria by measuring (i) the amount of active PDH (PDHa) and (ii) the rate of decarboxylation of alpha-[l-14C]oxoglutarate (at non-saturating [oxoglutarate]), at different concentrations of extramitochondrial Ca2+. In the presence of Na+ and Mg2+, both PDH and OGDH could be activated by increases in extramitochondrial [Ca2+] within the expected physiological range (0.05-5 microM). When liver mitochondria were prepared from rats treated with adrenaline, and then incubated in Na-free media containing EGTA, both PDH and OGDH activities were found to be enhanced. Evidence is presented that the activation of these enzymes by adrenaline is brought about by a mechanism involving increases in intramitochondrial [Ca2+].