Synchronization of calcium waves by mitochondrial substrates in Xenopus laevis oocytes

Nature. 1995 Oct 5;377(6548):438-41. doi: 10.1038/377438a0.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Animals
  • Calcium / metabolism*
  • Calcium-Transporting ATPases / metabolism
  • In Vitro Techniques
  • Indicators and Reagents / pharmacology
  • Inositol 1,4,5-Trisphosphate / metabolism*
  • Intracellular Membranes / metabolism
  • Malates / pharmacology
  • Membrane Potentials
  • Mitochondria / metabolism*
  • Oocytes
  • Oxidation-Reduction
  • Pyruvates / pharmacology
  • Pyruvic Acid
  • Signal Transduction
  • Succinates / pharmacology
  • Succinic Acid
  • Tetramethylphenylenediamine / pharmacology
  • Xenopus laevis


  • Indicators and Reagents
  • Malates
  • Pyruvates
  • Succinates
  • malic acid
  • Inositol 1,4,5-Trisphosphate
  • Pyruvic Acid
  • Adenosine Triphosphate
  • Succinic Acid
  • Calcium-Transporting ATPases
  • Tetramethylphenylenediamine
  • Calcium