Ca(2+) transfer from the ER to mitochondria: when, how and why

Biochim Biophys Acta. 2009 Nov;1787(11):1342-51. doi: 10.1016/j.bbabio.2009.03.015. Epub 2009 Mar 31.


The heterogenous subcellular distribution of a wide array of channels, pumps and exchangers allows extracellular stimuli to induce increases in cytoplasmic Ca(2+) concentration ([Ca(2+)]c) with highly defined spatial and temporal patterns, that in turn induce specific cellular responses (e.g. contraction, secretion, proliferation or cell death). In this extreme complexity, the role of mitochondria was considered marginal, till the direct measurement with targeted indicators allowed to appreciate that rapid and large increases of the [Ca(2+)] in the mitochondrial matrix ([Ca(2+)]m) invariably follow the cytosolic rises. Given the low affinity of the mitochondrial Ca(2+) transporters, the close proximity to the endoplasmic reticulum (ER) Ca(2+)-releasing channels was shown to be responsible for the prompt responsiveness of mitochondria. In this review, we will summarize the current knowledge of: i) the mitochondrial and ER Ca(2+) channels mediating the ion transfer, ii) the structural and molecular foundations of the signaling contacts between the two organelles, iii) the functional consequences of the [Ca(2+)]m increases, and iv) the effects of oncogene-mediated signals on mitochondrial Ca(2+) homeostasis. Despite the rapid progress carried out in the latest years, a deeper molecular understanding is still needed to unlock the secrets of Ca(2+) signaling machinery.

Publication types

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

MeSH terms

  • Adenosine Triphosphate / biosynthesis
  • Animals
  • Calcium / metabolism*
  • Calcium Channels / physiology
  • Calcium Signaling
  • Endoplasmic Reticulum / metabolism*
  • Humans
  • Inositol 1,4,5-Trisphosphate Receptors / physiology
  • Mitochondria / metabolism*
  • Proto-Oncogene Proteins c-akt / physiology
  • Proto-Oncogene Proteins c-bcl-2 / physiology
  • Voltage-Dependent Anion Channel 2 / physiology


  • Calcium Channels
  • Inositol 1,4,5-Trisphosphate Receptors
  • Proto-Oncogene Proteins c-bcl-2
  • Voltage-Dependent Anion Channel 2
  • mitochondrial calcium uniporter
  • Adenosine Triphosphate
  • Proto-Oncogene Proteins c-akt
  • Calcium