Sal1p, a calcium-dependent carrier protein that suppresses an essential cellular function associated With the Aac2 isoform of ADP/ATP translocase in Saccharomyces cerevisiae.
Adenine nucleotide translocase (Ant) catalyzes ADP/ATP exchange between the cytosol and the mitochondrial matrix. It is also proposed to form or regulate the mitochondrial permeability transition pore, a megachannel of high conductancy on the mitochondrial membranes. Eukaryotic genomes generally contain multiple isoforms of Ant. In this study, it is shown that the Ant isoforms are functionally differentiated in Saccharomyces cerevisiae. Although the three yeast Ant proteins can equally support respiration (the R function), Aac2p and Aac3p, but not Aac1p, have an additional physiological function essential for cell viability (the V function). The loss of V function in aac2 mutants leads to a lethal phenotype under both aerobic and anaerobic conditions. The lethality is suppressed by a strain-polymorphic locus, named SAL1 (for Suppressor of aac2 lethality). SAL1 was identified to encode an evolutionarily conserved protein of the mitochondrial carrier family. Notably, the Sal1 protein was shown to bind calcium through two EF-hand motifs located on its amino terminus. Calcium binding is essential for the suppressor activity. Finally, Sal1p is not required for oxidative phosphorylation and its overexpression does not complement the R(-) phenotype of aac2 mutants. On the basis of these observations, it is proposed that Aac2p and Sal1p may define two parallel pathways that transport a nucleotide substrate in an operational mode distinct from ADP/ATP exchange.
Chen
Xin Jie
XJ
Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9148, USA. xinjie.chen@utsouthwestern.edu
D000595:Amino Acid Sequence; D002352:Carrier Proteins / Q000235:genetics; D017124:Conserved Sequence; D006801:Humans; D007425:Intracellular Membranes / Q000502:physiology; D008564:Membrane Potentials; D008928:Mitochondria / Q000235:genetics / Q000502:physiology; D000226:Mitochondrial ADP, ATP Translocases / Q000235:genetics*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010641:Phenotype; D011487:Protein Conformation; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000254:growth & development; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics*; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid
D002352:Carrier Proteins; C112225:PET9 protein, S cerevisiae; C499805:SAL1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D000226:Mitochondrial ADP, ATP Translocases