title: Deletion of the transcriptional regulator opi1p decreases cardiolipin content and disrupts mitochondrial metabolism in Saccharomyces cerevisiae.
abstract: Cardiolipin, the main anionic phospholipid in the inner mitochondrial membrane, provides shape, charge and osmotic support to this membrane due to its biophysical properties. In addition, it helps form respiratory supercomplexes and provides functionality to mitochondrial proteins. Defects in the biosynthesis or remodeling of cardiolipin have been related to severe diseases, such as Barth syndrome. Opi1p, a transcriptional repressor for most enzymes in phospholipid biosynthesis found in Saccharomyces cerevisiae, has been demonstrated not to affect the biosynthesis of this mitochondrial phospholipid. However, we found that opi1 deletion compromises mitochondrial metabolism producing severe respiratory defects. The mechanism producing this phenotype was explored and found to be a mitochondrial cardiolipin depletion of almost 50%, resulting in low cytochrome content and high mitochondrial DNA instability. The origin of this low cardiolipin content strongly correlated with the overproduction of inositol, an intrinsic phenotype of this mutation. Overall, our results show that adequate regulation of phospholipid synthesis is essential for the maintenance of mitochondrial function.
authors.affiliation: Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, São Paulo, SP, Brazil. Electronic address: aluevano@iq.usp.br.
authors.forename: Luis Alberto
authors.initials: LA
authors.lastname: Luévano-Martínez
authors.forename: Patricia
authors.initials: P
authors.lastname: Appolinario
authors.forename: Sayuri
authors.initials: S
authors.lastname: Miyamoto
authors.forename: Salvador
authors.initials: S
authors.lastname: Uribe-Carvajal
authors.forename: Alicia J
authors.initials: AJ
authors.lastname: Kowaltowski
mesh_terms: D002308:Cardiolipins / Q000096:biosynthesis / Q000378:metabolism*; D004271:DNA, Fungal / Q000235:genetics; D004272:DNA, Mitochondrial / Q000235:genetics; D003576:Electron Transport Complex IV / Q000096:biosynthesis; D018628:Gene Dosage / Q000235:genetics; D042822:Genomic Instability / Q000235:genetics; D007294:Inositol / Q000096:biosynthesis / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism*; D051336:Mitochondrial Membranes / Q000378:metabolism; D025261:Mitochondrial Proton-Translocating ATPases / Q000096:biosynthesis; D006180:Proton-Translocating ATPases / Q000096:biosynthesis; D012097:Repressor Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*
chemical_list: C501004:ATP6 protein, S cerevisiae; D002308:Cardiolipins; D004271:DNA, Fungal; D004272:DNA, Mitochondrial; C096105:OPI1 protein, S cerevisiae; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D007294:Inositol; C526453:Cox1 protein, S cerevisiae; D003576:Electron Transport Complex IV; D025261:Mitochondrial Proton-Translocating ATPases; D006180:Proton-Translocating ATPases; C545198:Atp8 protein, S cerevisiae; C491522:OLI1 protein, S cerevisiae
keywords: Cardiolipin; Inositol; Membrane surface charge; Mitochondria; Phospholipids; Respiratory complexes