Fe2+ Induces a Transient Ca2+ Release from Rat Liver Mitochondria

Isolated mitochondria loaded with Ca2+ and then exposed to Fe2+ show a transient release of Ca2+. The magnitude of this response depends on the Ca2+ loading and the kinetics of the response depends on the concentration of added Fe2+. We investigated the Fe2+-induced Ca2+ release mechanism by measuring mitochondrial Ca2+ uptake in the presence of Fe2+. The presence of Fe2+ inhibits Ca2+ uptake two times. Since mitochondria can cycle Ca2+ across their inner membrane, the suppression of Ca2+ uptake, but not release, results in an elevation of the extramitochondrial Ca2+, thereby varying the steady state. The transient release of Ca2+ initially observed from mitochondria appears to occur via the electroneutral 2H+/Ca2+-exchange mechanism, since it can be markedly decreased by cyclosporin A and does not involve lipid peroxidation. When Fe2+ accumulation is completed, reuptake of released Ca2+ into mitochondria resumes. Finally, we propose that Fe2+ either inhibits Ca2+ entry at the uniporter or is transported by it into the matrix.