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Mitochondrial Ca2+ uptake pathways

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Abstract

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.

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Authors and Affiliations

  1. Department of Physiology and Biophysics, Faculty of Medicine, Dalhousie University, B3H 4R2, Halifax, NS, Canada

    Pia A. Elustondo

  2. Departments of Psychiatry and Pharmacology, Brain Repair Centre, Faculty of Medicine, Dalhousie University, B3H 4R2, Halifax, NS, Canada

    Matthew Nichols & George S. Robertson

  3. Department of Basic Sciences, College of Dentistry, New York University, 345 East 24th Street, New York, NY, 10010, USA

    Evgeny V. Pavlov

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  1. Pia A. Elustondo
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Correspondence to Evgeny V. Pavlov.

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Elustondo, P.A., Nichols, M., Robertson, G.S. et al. Mitochondrial Ca2+ uptake pathways. J Bioenerg Biomembr 49, 113–119 (2017). https://doi.org/10.1007/s10863-016-9676-6

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