Mitochondrial Ca2+ uptake pathways

Pia A. Elustondo, Matthew Nichols, George S. Robertson, Evgeny V. Pavlov

Research output: Contribution to journalReview articlepeer-review


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.

Original languageEnglish (US)
Pages (from-to)113-119
Number of pages7
JournalJournal of Bioenergetics and Biomembranes
Issue number1
StatePublished - Feb 1 2017


  • Calcium
  • Exchanger
  • Inorganic polyphosphate
  • Ion channel
  • Mitochondria
  • Permeability transition pore
  • Polyhydroxybutyrate
  • Uniporter

ASJC Scopus subject areas

  • Physiology
  • Cell Biology


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