Calcium and mitochondria in the regulation of cell death

Biochem Biophys Res Commun. 2015 Apr 24;460(1):72-81. doi: 10.1016/j.bbrc.2015.01.137.


The calcium ion has long been known to play an important role in cell death regulation. Hence, necrotic cell death was early associated with intracellular Ca(2+) overload, leading to mitochondrial permeability transition and functional collapse. Subsequent characterization of the signaling pathways in apoptosis revealed that Ca(2+)/calpain was critically involved in the processing of the mitochondrially localized, Apoptosis Inducing Factor. More recently, the calcium ion has been demonstrated to play important regulatory roles also in other cell death modalities, notably autophagic cell death and anoikis. In this review, we summarize current knowledge about the mechanisms involved in Ca(2+) regulation of these various modes of cell death with a focus on the importance of the mitochondria.

Keywords: Apoptosis; Autophagy; Calcium; Mitochondria; Necrosis; Reactive oxygen species.

Publication types

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

MeSH terms

  • Apoptosis / physiology*
  • Apoptosis Regulatory Proteins / metabolism*
  • Calcium / metabolism*
  • Calcium Signaling / physiology*
  • Calpain / metabolism
  • Mitochondria / physiology*
  • Mitochondrial Proteins / metabolism*
  • Models, Biological
  • Reactive Oxygen Species / metabolism*


  • Apoptosis Regulatory Proteins
  • Mitochondrial Proteins
  • Reactive Oxygen Species
  • Calpain
  • Calcium