Identification of mitochondrial carriers in Saccharomyces cerevisiae by transport assay of reconstituted recombinant proteins

Ferdinando Palmieri, Gennaro Agrimi, Emanuela Blanco, Alessandra Castegna, Maria A. Di Noia, Vito Iacobazzi, Francesco M. Lasorsa, C. M T Marobbio, Luigi Palmieri, Pasquale Scarcia, Simona Todisco, Angelo Vozza, John Walker

Research output: Contribution to journalReview articlepeer-review

Abstract

The inner membranes of mitochondria contain a family of carrier proteins that are responsible for the transport in and out of the mitochondrial matrix of substrates, products, co-factors and biosynthetic precursors that are essential for the function and activities of the organelle. This family of proteins is characterized by containing three tandem homologous sequence repeats of approximately 100 amino acids, each folded into two transmembrane α-helices linked by an extensive polar loop. Each repeat contains a characteristic conserved sequence. These features have been used to determine the extent of the family in genome sequences. The genome of Saccharomyces cerevisiae contains 34 members of the family. The identity of five of them was known before the determination of the genome sequence, but the functions of the remaining family members were not. This review describes how the functions of 15 of these previously unknown transport proteins have been determined by a strategy that consists of expressing the genes in Escherichia coli or Saccharomyces cerevisiae, reconstituting the gene products into liposomes and establishing their functions by transport assay. Genetic and biochemical evidence as well as phylogenetic considerations have guided the choice of substrates that were tested in the transport assays. The physiological roles of these carriers have been verified by genetic experiments. Various pieces of evidence point to the functions of six additional members of the family, but these proposals await confirmation by transport assay. The sequences of many of the newly identified yeast carriers have been used to characterize orthologs in other species, and in man five diseases are presently known to be caused by defects in specific mitochondrial carrier genes. The roles of eight yeast mitochondrial carriers remain to be established.

Original languageEnglish
Pages (from-to)1249-1262
Number of pages14
JournalBiochimica et Biophysica Acta - Bioenergetics
Volume1757
Issue number9-10
DOIs
Publication statusPublished - Sep 2006

Keywords

  • Mitochondria
  • Mitochondrial carrier
  • Proteomics
  • Saccharomyces cerevisiae
  • Transport
  • Transporter

ASJC Scopus subject areas

  • Biophysics

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