Pflügers Archiv

, Volume 447, Issue 5, pp 689–709 | Cite as

The mitochondrial transporter family (SLC25): physiological and pathological implications

  • Ferdinando PalmieriEmail author
The ABC of Solute Carriers Guest Editor: Matthias A. Hediger


The mitochondrial carriers (MCs) shuttle a variety of metabolites across the inner mitochondrial membrane (i.m.m.). In man they are encoded by the SLC25 genes. Some MCs have isoforms encoded by different SLC25 genes, whereas the phosphate carrier has two variants arising from an alternative splicing of SLC25A3. Six MCs have been sequenced after purification, and many more have been identified from their transport and kinetic properties following heterologous over-expression and reconstitution into liposomes. All MCs of known function belong to the same protein family, since their polypeptide chains consist of three tandemly related sequences of about 100 amino acids, and the repeats of the different carriers are homologous. They probably function as homodimers, each monomer being folded in the membrane into six transmembrane segments. The functional information obtained in studies with mitochondria and/or the reconstituted system has helped to gain an insight into the physiological role of the MCs in cell metabolism, as have tissue distribution, the use of knock-out mice (and/or yeast) and over-expression in human cell lines (or yeast) of individual carriers and isoforms. At the same time, the cloning and functional identification of many SLC25 genes has made it possible (i) to identify the genes (and their defects) responsible for some diseases, e.g. Stanley syndrome and Amish microcephaly, and (ii) where the genes were already known, to characterize the function of the gene products and hence understand the molecular basis and the symptoms of the diseases, e.g. hyperornithinaemia, hyperammonaemia and homocitrullinuria (HHH) syndrome and type II citrullinemia. It is likely that further extension and functional characterization of the SLC25 gene family will elucidate other diseases caused by MC deficiency.


Mitochondria Transport Transporters Carriers Solute carriers Mitochondrial diseases SLC25 genes Mitochondrial carrier genes Mitochondrial carrier family Physiological role of mitochondrial carriers 



ADP/ATP carrier


aspartate/glutamate carrier


peroxisomal adenine nucleotide carrier


bongkrekic acid


carnitine/acylcarnitine carrier




coenzyme A


citrate carrier


dicarboxylate carrier


deoxynucleotide carrier


glutamate carrier


Graves’ disease carrier


inner mitochondrial membrane


mitochondrial carrier


mitochondrial carrier family


(2-aminoethyl)-methanethiosulphonate hydrobromide




oxodicarboxylate carrier


oxoglutarate carrier


Online Mendelian Inheritance in Man (database)


ornithine carrier




phosphate carrier


name of the human mitochondrial solute carrier gene family, assigned by the Human Genome Organisation (HUGO) nomenclature committee


transmembrane segment


uncoupling protein



Research in the author’s laboratory was supported by grants from the Ministero dell’Istruzione, dell’Università e della Ricerca (MIUR), the Italian Consiglio Nazionale delle Ricerche (CNR), Centre of Excellence “Genomics: genes involved in pathopysiological processes in the biomedical and agricultural fields” (CEGBA), and the European Social Fund.


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Copyright information

© Springer-Verlag  2004

Authors and Affiliations

  1. 1.Department of Pharmaco-Biology, Laboratory of Biochemistry and Molecular BiologyUniversity of BariBariItaly

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