Mitochondrial Ca2+uptake pathways.
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.
Department of Physiology and Biophysics, Faculty of Medicine, Dalhousie University, B3H 4R2, Halifax, NS, Canada.
Pia A
PA
Elustondo
Departments of Psychiatry and Pharmacology, Brain Repair Centre, Faculty of Medicine, Dalhousie University, B3H 4R2, Halifax, NS, Canada.
Matthew
M
Nichols
Departments of Psychiatry and Pharmacology, Brain Repair Centre, Faculty of Medicine, Dalhousie University, B3H 4R2, Halifax, NS, Canada.
George S
GS
Robertson
Department of Basic Sciences, College of Dentistry, New York University, 345 East 24th Street, New York, NY, 10010, USA. ep37@nyu.edu.
Evgeny V
EV
Pavlov
D002118:Calcium / Q000378:metabolism* / Q000502:physiology; D017136:Ion Transport; D053858:Metabolic Networks and Pathways; D008928:Mitochondria / Q000378:metabolism*; D008933:Mitochondrial Swelling
D002118:Calcium
Calcium; Exchanger; Inorganic polyphosphate; Ion channel; Mitochondria; Permeability transition pore; Polyhydroxybutyrate; Uniporter
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