Quasi-synaptic calcium signal transmission between endoplasmic reticulum and mitochondria

György Csordás, Andrew P. Thomas, György Hajnóczky

Research output: Contribution to journalArticlepeer-review

419 Scopus citations


Transmission of cytosolic [Ca2+] ([Ca2+](c)) oscillations into the mitochondrial matrix is thought to be supported by local calcium control between IP3 receptor Ca2+ channels (IP3R) and mitochondria, but study of the coupling mechanisms has been difficult. We established a permeabilized cell model in which the Ca2+ coupling between endoplasmic reticulum (ER) and mitochondria is retained, and mitochondrial [Ca2+] ([Ca2+](m)) can be monitored by fluorescence imaging. We demonstrate that maximal activation of mitochondrial Ca2+ uptake is evoked by IP3-induced perimitochondrial [Ca2+] elevations, which appear to reach values > 20-fold higher than the global increases of [Ca2+](c). Incremental doses of IP3 elicited [Ca2+], elevations that followed the quantal pattern of Ca2+ mobilization, even at the level of individual mitochondria. In contrast, gradual increases of IP3 evoked relatively small [Ca2+](m) responses despite eliciting similar [Ca2+](c) increases. We conclude that each mitochondrial Ca2+ uptake site faces multiple IP3R, a concurrent activation of which is required for optimal activation of mitochondrial Ca2+ uptake. This architecture explains why calcium oscillations evoked by synchronized periodic activation of IP3R are particularly effective in establishing dynamic control over mitochondrial metabolism, Furthermore, our data reveal fundamental functional similarities between ER-mitochondrial Ca2+ coupling and synaptic transmission.

Original languageEnglish (US)
Pages (from-to)96-108
Number of pages13
JournalEMBO Journal
Issue number1
StatePublished - Jan 4 1999
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)


  • Calcium signal
  • Endoplasmic reticulum
  • Inositol trisphosphate
  • Mitochondria
  • Quantal calcium release

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