Molecular regulation of MCU: Implications in physiology and disease

Cell Calcium. 2018 Sep:74:86-93. doi: 10.1016/j.ceca.2018.06.006. Epub 2018 Jun 27.

Abstract

Ca2+ flux across the inner mitochondrial membrane (IMM) regulates cellular bioenergetics, intra-cellular cytoplasmic Ca2+ signals, and various cell death pathways. Ca2+ entry into the mitochondria occurs due to the highly negative membrane potential (ΔΨm) through a selective inward rectifying MCU channel. In addition to being regulated by various mitochondrial matrix resident proteins such as MICUs, MCUb, MCUR1 and EMRE, the channel is transcriptionally regulated by upstream Ca2+ cascade, post transnational modification and by divalent cations. The mode of regulation either inhibits or enhances MCU channel activity and thus regulates mitochondrial metabolism and cell fate.

Keywords: Calcium; Channel; EMRE; MCU; MCUR1; MCUb; MICU1; Magnesium; MiST; Miro1; Mitochondria; Oxidants; SLC25A23.

Publication types

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

MeSH terms

  • Animals
  • Calcium / metabolism*
  • Calcium Channels / chemistry
  • Calcium Channels / metabolism*
  • Cell Death / physiology
  • Cell Physiological Phenomena / physiology*
  • Cytosol / metabolism
  • Humans
  • Membrane Potential, Mitochondrial / physiology
  • Mitochondria / metabolism
  • Mitochondrial Membrane Transport Proteins / chemistry
  • Mitochondrial Membrane Transport Proteins / metabolism
  • Mitochondrial Membranes / metabolism*

Substances

  • Calcium Channels
  • Mitochondrial Membrane Transport Proteins
  • mitochondrial calcium uniporter
  • Calcium