Synchronization of calcium waves by mitochondrial substrates in Xenopus laevis oocytes.
In Xenopus oocytes, as well as other cells, inositol-1,4,5-trisphosphate (Ins(1,4,5)P3)-induced Ca2+ release is an excitable process that generates propagating Ca2+ waves that annihilate upon collision. The fundamental property responsible for excitability appears to be the Ca2+ dependency of the Ins(1,4,5)P3 receptor. Here we report that Ins(1,4,5)P3-induced Ca2+ wave activity is strengthened by oxidizable substrates that energize mitochondria, increasing Ca2+ wave amplitude, velocity and interwave period. The effects of pyruvate/malate are blocked by ruthenium red at the Ca2+ uniporter, by rotenone at complex I, and by antimycin A at complex III, and are subsequently rescued at complex IV by ascorbate tetramethylphenylenediamine (TMPD). Our data reveal that potential-driven mitochondrial Ca2+ uptake is a major factor in the regulation of Ins(1,4,5)P3-induced Ca2+ release and clearly demonstrate a physiological role of mitochondria in intracellular Ca2+ signalling.
Jouaville
L S
LS
Department of Neuroscience, University of Virginia, Charlottesville 22908, USA.
Ichas
F
F
Holmuhamedov
E L
EL
Camacho
P
P
Lechleiter
J D
JD
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D066298:In Vitro Techniques; D007202:Indicators and Reagents / Q000494:pharmacology; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism*; D007425:Intracellular Membranes / Q000378:metabolism; D008293:Malates / Q000494:pharmacology; D008564:Membrane Potentials; D008928:Mitochondria / Q000378:metabolism*; D009865:Oocytes; D010084:Oxidation-Reduction; D011773:Pyruvates / Q000494:pharmacology; D019289:Pyruvic Acid; D015398:Signal Transduction; D013386:Succinates / Q000494:pharmacology; D019802:Succinic Acid; D013772:Tetramethylphenylenediamine / Q000494:pharmacology; D014982:Xenopus laevis
D007202:Indicators and Reagents; D008293:Malates; D011773:Pyruvates; D013386:Succinates; C030298:malic acid; D015544:Inositol 1,4,5-Trisphosphate; D019289:Pyruvic Acid; D000255:Adenosine Triphosphate; D019802:Succinic Acid; D000252:Calcium-Transporting ATPases; D013772:Tetramethylphenylenediamine; D002118:Calcium