The recent discovery of genes encoding the mitochondrial calcium (Ca2+) uniporter has revealed new opportunities for studying how abnormal Ca2+signals cause disease. Ca2+transport across the mitochondrial inner membrane is highly regulated, and the uniporter is the channel that acts as a major portal for Ca2+influx. Low amounts of mitochondrial Ca2+can boost ATP synthesis, but excess amounts, such as following cytoplasmic Ca2+overload in heart failure, triggers mitochondrial failure and cell death. In fact, precisely because mitochondrial Ca2+transport is so tightly regulated, a fundamental understanding of how the uniporter functions is necessary. Two key uniporter features allow Ca2+influx without mitochondrial damage during normal physiology. First, the channel is significantly more selective than other known Ca2+channels. This prevents the permeation of other ions and uncoupling of the electrochemical gradient. Second, the uniporter becomes active at only high Ca2+concentrations, preventing a resting leak of cytoplasmic Ca2+itself. Now possessing the identities of the various proteins forming the uniporter, we can proceed with efforts to define the molecular determinants of permeation, selectivity and Ca2+- regulation. ©2014 Elsevier Inc. All rights reserved.
Mendeley saves you time finding and organizing research
Choose a citation style from the tabs below