TcBid promotes Ca2+ signal propagation to the mitochondria: Control of Ca2+ permeation through the outer mitochondrial membrane

György Csordás, Muniswamy Madesh, Bruno Antonsson, György Hajnóczky

Research output: Contribution to journalArticlepeer-review

76 Scopus citations


Calcium spikes established by IP3 receptor-mediated Ca2+ release from the endoplasmic reticulum (ER) are transmitted effectively to the mitochondria, utilizing local Ca2+ interactions between closely associated subdomains of the ER and mitochondria. Since the outer mitochondrial membrane (OMM) has been thought to be freely permeable to Ca2+, investigations have focused on IP3-driven Ca2+ transport through the inner mitochondrial membrane (IMM). Here we demonstrate that selective permeabilization of the OMM by tcBid, a proapoptotic protein, results in an increase in the magnitude of the IP3-induced mitochondrial [Ca2+] signal. This effect of tcBid was due to promotion of activation of Ca2+ uptake sites in the IMM and, in turn, to facilitation of mitochondrial Ca2+ uptake. In contrast, tcBid failed to control the delivery of sustained and global Ca2+ signals to the mitochondria. Thus, our data support a novel model that Ca2+ permeability of the OMM at the ER-mitochondrial interface is an important determinant of local Ca2+ signalling. Facilitation of Ca2+ delivery to the mitochondria by tcBid may also support recruitment of mitochondria to the cell death machinery.

Original languageEnglish (US)
Pages (from-to)2198-2206
Number of pages9
JournalEMBO Journal
Issue number9
StatePublished - May 1 2002
Externally publishedYes


  • Apoptosis
  • Bid
  • Calcium
  • Mitochondria
  • Outer mitochondrial membrane

ASJC Scopus subject areas

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


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