Synchronization of calcium waves by mitochondrial substrates in Xenopus laevis oocytes
Nature. 1995-10-01; 377(6548): 438-441
DOI: 10.1038/377438a0
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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.