Cyclosporin A (CsA) is a well-known inhibitor of prooxidant-induced mitochondrial Ca2+ release and apoptosis in mammalian cells. CsA also protects plants against programmed cell death by an unknown mechanism. In this study, we examined the effects of CsA on Ca2+ transport by mitochondria isolated from cultured Citrus sinensis Obs. cv. Pera cells. CsA inhibited Ca2+ uptake by Citrus mitochondria in a concentration-dependent manner, but did not affect ruthenium red-induced Ca2+ release. CsA also prevented the decrease in mitochondrial membrane potential and the uncoupling of respiratory activity resulting from Ca2+ uptake. As expected, CsA did not affect Ca2+ influx in rat liver mitochondria. These results indicate a difference in the Ca2+ transport systems of plant and animal mitochondria. The inhibitory action of CsA on Ca2+ uptake by Citrus mitochondria could explain the ability of this drug to prevent plant programmed cell death, a process that can be triggered by mitochondrial Ca2+ loading. (c) 2006 Elsevier Ireland Ltd. All rights reserved.1723665670