Mitochondrial Ca2+ signaling

Pharmacol Ther. 2018 Dec;192:112-123. doi: 10.1016/j.pharmthera.2018.07.001. Epub 2018 Jul 20.


Mitochondrial Ca2+ regulation is crucial for bioenergetics and cellular signaling. The mechanisms controlling mitochondrial calcium homeostasis have been recently unraveled with the discovery of mitochondrial inner membrane proteins that regulate mitochondrial Ca2+ uptake and extrusion. Mitochondrial Ca2+ uptake depends on a large complex of proteins centered around the Ca2+ channel protein, mitochondrial Ca2+ uniporter (MCU) in close interactions with several regulatory subunits (MCUb, EMRE, MICU1, MICU2). Mitochondrial Ca2+ extrusion is mainly mediated by the mitochondrial Na+/Ca2+/Li+ exchanger (NCLX). Here, we review the major players of mitochondrial Ca2+ homeostasis and their physiological functions.

Keywords: Ca(2+) signaling; Cell metabolism; MCU; Mitochondria associated membranes; NCLX; Reactive oxygen species; physiology of mitochondrial Ca(2+).

Publication types

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

MeSH terms

  • Animals
  • Calcium Channels / metabolism*
  • Calcium Signaling / physiology*
  • Energy Metabolism
  • Homeostasis
  • Humans
  • Intracellular Membranes / metabolism*
  • Mitochondria / metabolism*


  • Calcium Channels
  • mitochondrial calcium uniporter