After Half a Century Mitochondrial Calcium In- And Efflux Machineries Reveal Themselves

EMBO J. 2011 Sep 20;30(20):4119-25. doi: 10.1038/emboj.2011.337.


Mitochondrial Ca(2+) uptake and release play a fundamental role in the control of different physiological processes, such as cytoplasmic Ca(2+) signalling, ATP production and hormone metabolism, while dysregulation of mitochondrial Ca(2+) handling triggers the cascade of events that lead to cell death. The basic mechanisms of mitochondrial Ca(2+) homeostasis have been firmly established for decades, but the molecular identities of the channels and transporters responsible for Ca(2+) uptake and release have remained mysterious until very recently. Here, we briefly review the main findings that have led to our present understanding of mitochondrial Ca(2+) homeostasis and its integration in cell physiology. We will then discuss the recent work that has unravelled the biochemical identity of three key molecules: NCLX, the mitochondrial Na(+)/Ca(2+) antiporter, MCU, the pore-forming subunit of the mitochondrial Ca(2+) uptake channel, and MICU1, one of its regulatory subunits.

Publication types

  • Review

MeSH terms

  • Animals
  • Calcium / metabolism*
  • Calcium Channels / metabolism*
  • Calcium Signaling / physiology
  • Mitochondria / metabolism*
  • Mitochondrial Membranes / metabolism
  • Rats
  • Sodium-Calcium Exchanger / metabolism*


  • Calcium Channels
  • Sodium-Calcium Exchanger
  • Calcium