Pflügers Archiv

, Volume 447, Issue 5, pp 689–709

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

The ABC of Solute Carriers Guest Editor: Matthias A. Hediger

DOI: 10.1007/s00424-003-1099-7

Cite this article as:
Palmieri, F. Pflugers Arch - Eur J Physiol (2004) 447: 689. doi:10.1007/s00424-003-1099-7

Abstract

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.

Keywords

MitochondriaTransportTransportersCarriersSolute carriersMitochondrial diseasesSLC25 genesMitochondrial carrier genesMitochondrial carrier familyPhysiological role of mitochondrial carriers

Abbreviations

AAC

ADP/ATP carrier

AGC

aspartate/glutamate carrier

ANC

peroxisomal adenine nucleotide carrier

BKA

bongkrekic acid

CAC

carnitine/acylcarnitine carrier

CATR

carboxyatractyloside

CoA

coenzyme A

CIC

citrate carrier

DIC

dicarboxylate carrier

DNC

deoxynucleotide carrier

GC

glutamate carrier

GDC

Graves’ disease carrier

i.m.m.

inner mitochondrial membrane

MC

mitochondrial carrier

MCF

mitochondrial carrier family

MTSEA

(2-aminoethyl)-methanethiosulphonate hydrobromide

OAA

oxaloacetate

ODC

oxodicarboxylate carrier

OGC

oxoglutarate carrier

OMIM

Online Mendelian Inheritance in Man (database)

ORC

ornithine carrier

PEP

phosphoenolpyruvate

PiC

phosphate carrier

SLC25

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

TMS

transmembrane segment

UCP

uncoupling protein

Copyright information

© Springer-Verlag  2004

Authors and Affiliations

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