Calcium uptake mechanisms of mitochondria.
The ability of mitochondria to capture Ca2+ ions has important functional implications for cells, because mitochondria shape cellular Ca2+ signals by acting as a Ca2+ buffer and respond to Ca2+ elevations either by increasing the cell energy supply or by triggering the cell death program of apoptosis. A mitochondrial Ca2+ channel known as the uniporter drives the rapid and massive entry of Ca2+ ions into mitochondria. The uniporter operates at high, micromolar cytosolic Ca2+ concentrations that are only reached transiently in cells, near Ca2+ release channels. Mitochondria can also take up Ca2+ at low, nanomolar concentrations, but this high affinity mode of Ca2+ uptake is not well characterized. Recently, leucine-zipper-EF hand-containing transmembrane region (Letm1) was proposed to be an electrogenic 1:1 mitochondrial Ca2+/H+ antiporter that drives the uptake of Ca2+ into mitochondria at nanomolar cytosolic Ca2+ concentrations. In this article, we will review the properties of the Ca2+ import systems of mitochondria and discuss how Ca2+ uptake via an electrogenic 1:1 Ca2+/H+ antiport challenges our current thinking of the mitochondrial Ca2+ uptake mechanism.
Santo-Domingo
Jaime
J
Department of Cell Physiology and Metabolism, University of Geneva, 1, rue Michel-Servet, CH-1211 Geneva 4, Switzerland.
Demaurex
Nicolas
N
D000818:Animals; D017920:Antiporters / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism; D020013:Calcium Signaling; D002135:Calcium-Binding Proteins / Q000378:metabolism; D027682:Cation Transport Proteins / Q000378:metabolism; D006801:Humans; D017136:Ion Transport; D008565:Membrane Proteins / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism*; D008954:Models, Biological
D017920:Antiporters; D015220:Calcium Channels; D002135:Calcium-Binding Proteins; D027682:Cation Transport Proteins; C488528:LETM1 protein, human; D008565:Membrane Proteins; C027614:calcium-hydrogen antiporters; C034703:mitochondrial calcium uniporter; D002118:Calcium