Mitochondrial Citrate Transporters Ctp1-Yhm2 and Respiratory Chain: A Coordinated Functional Connection in Saccharomyces Cerevisiae Metabolism

The mitochondrial inner membrane contains some hydrophobic proteins that mediate the exchange of metabolites between the mitochondrial matrix and the cytosol. Ctp1 and Yhm2 are two carrier proteins in the yeast Saccharomyces cerevisiae responsible for the transport of citrate, a tricarboxylate involved in several metabolic pathways.Since these proteins also contribute to respiratory metabolism, in this study we investigated for the first time whether changes in citrate transport can affect the structural organization and functional properties of respiratory complexes.Through experiments in yeast mutant cells in which the gene encoding Ctp1 or Yhm2 was deleted, we found that in the absence of either mitochondrial citrate transporter, mitochondrial respiration was impaired. Structural analysis of the respiratory complexes III and IV revealed different expression levels of the catalytic and supernumerary subunits in the Δctp1 and Δyhm2 strains. In addition, Δyhm2 mitochondria appeared to be more sensitive than Δctp1 to the oxidative damage.Our results provide the first evidence for a coordinated modulation of mitochondrial citrate transport and respiratory chain activity in S. cerevisiae metabolism.