title: Discoveries, metabolic roles and diseases of mitochondrial carriers: A review.
abstract: Mitochondrial carriers (MCs) are a superfamily of nuclear-encoded proteins that are mostly localized in the inner mitochondrial membrane and transport numerous metabolites, nucleotides, cofactors and inorganic anions. Their unique sequence features, i.e., a tripartite structure, six transmembrane α-helices and a three-fold repeated signature motif, allow MCs to be easily recognized. This review describes how the functions of MCs from Saccharomyces cerevisiae, Homo sapiens and Arabidopsis thaliana (listed in the first table) were discovered after the genome sequence of S. cerevisiae was determined in 1996. In the genomic era, more than 50 previously unknown MCs from these organisms have been identified and characterized biochemically using a method consisting of gene expression, purification of the recombinant proteins, their reconstitution into liposomes and transport assays (EPRA). Information derived from studies with intact mitochondria, genetic and metabolic evidence, sequence similarity, phylogenetic analysis and complementation of knockout phenotypes have guided the choice of substrates that were tested in the transport assays. In addition, the diseases associated to defects of human MCs have been briefly reviewed. This article is part of a Special Issue entitled: Mitochondrial Channels edited by Pierre Sonveaux, Pierre Maechler and Jean-Claude Martinou.
authors.affiliation: Department of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari, Via E. Orabona 4, 70125 Bari, Italy. Electronic address: ferdpalmieri@gmail.com.
authors.forename: Ferdinando
authors.initials: F
authors.lastname: Palmieri
authors.affiliation: Department of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari, Via E. Orabona 4, 70125 Bari, Italy; Department of Sciences, University of Basilicata, Via Ateneo Lucano 10, 85100 Potenza, Italy.
authors.forename: Magnus
authors.initials: M
authors.lastname: Monné
mesh_terms: D000818:Animals; D029681:Arabidopsis Proteins / Q000378:metabolism; D001692:Biological Transport; D015870:Gene Expression; D006801:Humans; D008928:Mitochondria / Q000378:metabolism*; D028361:Mitochondrial Diseases / Q000235:genetics / Q000378:metabolism; D033681:Mitochondrial Membrane Transport Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D051336:Mitochondrial Membranes / Q000378:metabolism; D010802:Phylogeny; D000072417:Protein Domains; D011994:Recombinant Proteins / Q000302:isolation & purification / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000502:physiology
chemical_list: D029681:Arabidopsis Proteins; D033681:Mitochondrial Membrane Transport Proteins; D011994:Recombinant Proteins; D029701:Saccharomyces cerevisiae Proteins
keywords: Mitochondria; Mitochondrial carrier; Mitochondrial carrier-associated diseases; Mitochondrial transporter; SLC25; Transport