Calcium and apoptosis: ER-mitochondria Ca2+ transfer in the control of apoptosis

Oncogene. 2008 Oct 27;27(50):6407-18. doi: 10.1038/onc.2008.308.

Abstract

There is a growing consensus that the various forms of cell death (necrosis, apoptosis and autophagy) are not separated by strict boundaries, but rather share molecular effectors and signaling routes. Among the latter, a clear role is played by calcium (Ca(2+)), the ubiquitous second messenger involved in the control of a broad variety of physiological events. Fine tuning of intracellular Ca(2+) homeostasis by anti- and proapoptotic proteins shapes the Ca(2+) signal to which mitochondria and other cellular effectors are exposed, and hence the efficiency of various cell death inducers. Here, we will review: (i) the evidence linking calcium homeostasis to the regulation of apoptotic, and more recently autophagic cell death, (ii) the discussion of mitochondria as a critical, although not unique checkpoint and (iii) the molecular and functional elucidation of ER/mitochondria contacts, corresponding to the mitochondria-associated membrane (MAM) subfraction and proposed to be a specialized signaling microdomain.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Apoptosis / physiology*
  • Calcium / metabolism
  • Calcium / physiology*
  • Cytosol / metabolism
  • Endoplasmic Reticulum / metabolism*
  • Humans

Substances

  • Calcium