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Luevano-Martinez, Luis Alberto; Appolinario, Patricia; Miyamoto, Sayuri; Uribe-Carvajal, Salvador; Kowaltowski, Alicia J (2013)

DELETION OF THE TRANSCRIPTIONAL REGULATOR OPI1P DECREASES CARDIOLIPIN CONTENT AND DISRUPTS MITOCHONDRIAL METABOLISM IN SACCHAROMYCES CEREVISIAE

Fungal Genet. Biol. 60(SI):150-158
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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.