Fe(2+) induces a transient Ca(2+) release from rat liver mitochondria.
Isolated mitochondria loaded with Ca(2+) and then exposed to Fe(2+) show a transient release of Ca(2+). The magnitude of this response depends on the Ca(2+) loading and the kinetics of the response depends on the concentration of added Fe(2+). We investigated the Fe(2+)-induced Ca(2+) release mechanism by measuring mitochondrial Ca(2+) uptake in the presence of Fe(2+). The presence of Fe(2+) inhibits Ca(2+) uptake two times. Since mitochondria can cycle Ca(2+) across their inner membrane, the suppression of Ca(2+) uptake, but not release, results in an elevation of the extramitochondrial Ca(2+), thereby varying the steady state. The transient release of Ca(2+) initially observed from mitochondria appears to occur via the electroneutral 2H(+)/Ca(2+)-exchange mechanism, since it can be markedly decreased by cyclosporin A and does not involve lipid peroxidation. When Fe(2+) accumulation is completed, reuptake of released Ca(2+) into mitochondria resumes. Finally, we propose that Fe(2+) either inhibits Ca(2+) entry at the uniporter or is transported by it into the matrix.
Gogvadze
Vladimir
V
Department of Molecular and Cell Biology, University of California, Berkeley, California 94720, USA.
Walter
Patrick B
PB
Ames
Bruce N
BN
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D017136:Ion Transport / Q000187:drug effects; D007501:Iron / Q000378:metabolism* / Q000494:pharmacology; D008930:Mitochondria, Liver / Q000378:metabolism*; D051381:Rats
D007501:Iron; D002118:Calcium