Mitochondrial calcium transport and the redox nature of the calcium-induced membrane permeability transition

Abstract

Mitochondria possess a Ca²⁺ transport system composed of separate Ca²⁺ influx and efflux pathways. Intramitochondrial Ca²⁺ concentrations regulate oxidative phosphorylation, required for cell function and survival, and mitochondrial redox balance, that participates in a myriad of signaling and damaging pathways. The interaction between Ca²⁺ accumulation and redox imbalance regulates opening and closing of a highly regulated inner membrane pore, the membrane permeability transition pore (PTP). In this review, we discuss the regulation of the PTP by mitochondrial oxidants, reactive nitrogen species, and the interactions between these species and other PTP inducers. In addition, we discuss the involvement of mitochondrial redox imbalance and PTP in metabolic conditions such as atherogenesis, diabetes, obesity and in mtDNA stability.