Synchronization of calcium waves by mitochondrial substrates in Xenopus laevis oocytes

INXenopus oocytes, as well as other cells, inositol-l,4,5-tris-phosphate (Ins(l,4,5)P₃)-induced Ca²⁺ release^1-4 is an excitable process that generates propagating Ca²⁺ waves^5-7 that annihilate upon collision^8-12. The fundamental property responsible for excitability¹³ appears to be the Ca²⁺ dependency of the Ins(l,4,5)P₃ receptor⁹. Here we report that Ins(l,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)¹⁴. Our data reveal that potential-driven mitochondrial Ca²⁺ uptake is a major factor in the regulation of Ins(l,4,5)P₃-induced Ca²⁺ release and clearly demonstrate a physiological role of mitochondria in intracellular Ca²⁺ signalling.