Direct interaction of Saccharomyces cerevisiae Faa1p with the Omi/HtrA protease orthologue Ynm3p alters lipid homeostasis

Abstract

In yeast, long chain acyl-CoA synthetase (ACSL) activity is required for fatty acid uptake, metabolism and fatty acid-dependent transcriptional control. The major ACSL contributing these functions is Faa1p. In a yeast two-hybrid screen, the Omi/HtrA serine protease family orthologue Ynm3p (YNL123w) was identified as a specific interactor with Faa1p. Interaction of Ynm3p and Faa1p was confirmed by co-immunoprecipitation. Disruption of the YNM3 gene encoding Ynm3p resulted in increased fatty acid uptake, triglyceride accumulation and reduced expression of the fatty acid-responsive OLE1 gene encoding the essential Δ⁹-acyl-CoA desaturase. These changes were linked with increased Faa1p and Faa4p ACSL activities. We propose that Ynm3p modulates fatty acid metabolism and gene regulation through negative regulation of ACSL activity. Additional strain-specific phenotypes associated with deletion of YNM3 included inability to grow on non-fermentable carbon sources and altered cellular morphology.