The effect of oxaloacetate on Ca2+ transport by isolated rat liver mit
ochondria has been studied Under aerobic conditions mitochondria incub
ated in the presence of oxaloacetate (OA) accumulated Ca2+ in a Ruthen
ium Red (RR) and uncoupler sensitive manner. Oxaloacetate in the prese
nce of inhibitors of the respiratory chain and ATPase also supports sl
ow accumulation (5 nmoles/mg protein per min) of a limited amount of c
alcium by mitochondria. Under these conditions ADP, pyruvate, succinat
e, and isocitrate increase both the rate of OA-dependent calcium trans
port and the amount of calcium accumulated In all cases (excepting iso
citrate) OA-dependent Ca2+ accumulation is blocked by low arsenite con
centrations. Addition of OA to mitochondria treated by inhibitors of t
he respiratory chain and ATPase increases [NAD(+)].[NADPH]I[NADH].[NAD
P(+)] and mitochondrial transmembrane potential generation. Ammonium c
hloride decreases the rate of oxaloacetate-dependent calcium accumulat
ion. The data presented suggest that mitochondrial OA-dependent Ca2+ a
ccumulation first described here is mediated by energy-dependent mitoc
hondrial transhydrogenase. The data are discussed in accordance with t
he problem of OA-induced calcium release.