Effect of cytosolic Mg2+ on mitochondrial Ca2+ signaling.
Cytosolic Ca2+ signals are followed by mitochondrial Ca2+ uptake, which, in turn, modifies several biological processes. Mg2+ is known to inhibit Ca2+ uptake by isolated mitochondria, but its significance in intact cells has not been elucidated. In HEK293T cells, activation of purinergic receptors with extracellular ATP caused cytosolic Ca2+ signals associated with parallel changes in cytosolic [Mg2+]. Neither signals were affected by omitting bivalent cations from the extracellular medium. The effect of store-operated Ca2+ influx on cytosolic Mg2+ concentration ([Mg2+]c) was negligible. Uncaged Ca2+ displaced Mg2+ from cytosolic binding sites, but for an equivalent Ca2+ signal, the change in [Mg2+] was significantly smaller than that measured after adding extracellular ATP. Inositol 1,4,5-trisphosphate mobilized Ca2+ and Mg2+ from internal stores in permeabilized cells. The increase of [Mg2+] in the range that occurred in ATP-stimulated cells inhibited mitochondrial Ca2+ uptake in permeabilized cells without affecting mitochondrial Ca2+ efflux. Therefore, the Mg2+ signal generated by Ca2+ mobilizing agonists may attenuate mitochondrial Ca2+ uptake.
Szanda
Gergo
G
Department of Physiology, Faculty of Medicine, Semmelweis University, P.O. Box 259, 1444, Budapest, Hungary.
Rajki
Anikó
A
Gallego-Sandín
Sonia
S
Garcia-Sancho
Javier
J
Spät
András
A
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000502:physiology*; D002460:Cell Line; D003593:Cytoplasm / Q000378:metabolism*; D006801:Humans; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D008274:Magnesium / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism*
D015544:Inositol 1,4,5-Trisphosphate; D000255:Adenosine Triphosphate; D008274:Magnesium; D002118:Calcium