Published Online: 15 MAR 2013
Copyright © 2001 John Wiley & Sons, Ltd. All rights reserved.
How to Cite
del Arco, A. and Satrústegui, J. 2013. Mitochondrial Carriers. eLS. .
- Published Online: 15 MAR 2013
In eukaryotic cells, the exchange of metabolites across the inner mitochondrial membrane is performed by members of the mitochondrial carrier family (MCF), the largest family of solute transporters. Mutations in MCF genes are associated with rare genetic diseases underscoring the relevance of individual MCF members. Mitochondrial carriers have a common tripartite structure made up by tandem repeats of 100 amino acids each containing two transmembrane α-helices and one conserved MCF signature. MCF members are present in two states, c and m, with binding sites for substrates facing either the intermembrane (c) or matrix (m) space. X-ray crystallography of the mitochondrial ADP/ATP carrier in the c-state has shown that the six α-helices form a compact bundle shaping a cavity sealed on the matrix side by a salt-bridge network. Substrate binding perturbs the salt-bridge network triggering conformational changes that cause the opening of the carrier towards the matrix coupled to substrate transport.
Mitochondrial carriers perform the exchange of metabolites, nucleotides and cofactors through the inner mitochondrial membrane.
Mitochondrial carriers form an evolutionary conserved family present in all eukaryotic cells.
Mitochondrial carriers share a tripartite structure made up by repeats of 100 amino acids containing two α-helices connected by a hydrophilic loop.
Phylogenetic analyses have shown the existence of a limited number of mitochondrial carrier subfamilies involved in the transport of structurally related substrates.
Mutations in nine mitochondrial carriers cause autosomal recessive disorders in humans.
Mitochondrial carriers are present in either one of two different states, c and m, in which binding sites for substrates face the intermembrane (c) or matrix (m) spaces.
During the transport cycle, substrate binding in each of these states induces a transition to the other state which is coupled to substrate transport.
The three-dimensional structure solved for the ADP/ATP carrier in the c state is consistent with a bundle of six transmembrane α-helices forming an aqueous cavity closed towards the matrix by electrostatic interactions. Specific interactions of substrates with the substrate-binding site within the aqueous cavity will disturb the electrostatic interactions that maintain the carrier closed to the matrix side.
Substrate translocation by mitochondrial carriers occurs coupled to conformational movements of the α-helices that open the carrier.
- solute transport;
- human diseases