Mitochondrial Ca2+ uptake pathways

J Bioenerg Biomembr. 2017 Feb;49(1):113-119. doi: 10.1007/s10863-016-9676-6. Epub 2016 Sep 24.


Calcium (Ca2+) plays diverse roles in all living organisms ranging from bacteria to humans. It is a structural element for bones, an essential mediator of excitation-contraction coupling, and a universal second messenger in the regulation of ion channel, enzyme and gene expression activities. In mitochondria, Ca2+ is crucial for the control of energy production and cellular responses to metabolic stress. Ca2+ uptake by the mitochondria occurs by the uniporter mechanism. The Mitochondrial Ca2+ Uniporter (MCU) protein has recently been identified as a core component responsible for mitochondrial Ca2+ uptake. MCU knockout (MCU KO) studies have identified a number of important roles played by this high capacity uptake pathway. Interestingly, this work has also shown that MCU-mediated Ca2+ uptake is not essential for vital cell functions such as muscle contraction, energy metabolism and neurotransmission. Although mitochondrial Ca2+ uptake was markedly reduced, MCU KO mitochondria still contained low but detectable levels of Ca2+. In view of the fundamental importance of Ca2+ for basic cell signalling, this finding suggests the existence of other currently unrecognized pathways for Ca2+ entry. We review the experimental evidence for the existence of alternative Ca2+ influx mechanisms and propose how these mechanisms may play an integral role in mitochondrial Ca2+ signalling.

Keywords: Calcium; Exchanger; Inorganic polyphosphate; Ion channel; Mitochondria; Permeability transition pore; Polyhydroxybutyrate; Uniporter.

Publication types

  • Review

MeSH terms

  • Calcium / metabolism*
  • Calcium / physiology
  • Ion Transport*
  • Metabolic Networks and Pathways
  • Mitochondria / metabolism*
  • Mitochondrial Swelling


  • Calcium