Direct interaction of Saccharomyces cerevisiae Faa1p with the Omi/HtrA protease orthologue Ynm3p alters lipid homeostasis.
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 Delta(9)-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.
Center for Metabolic Disease, Ordway Research Institute, Inc., 150 New Scotland Avenue, Albany, NY 12208-3425, USA.
Fumin
F
Tong
Paul N
PN
Black
Lori
L
Bivins
Steven
S
Quackenbush
Vlasta
V
Ctrnacta
Concetta C
CC
DiRusso
D000214:Acyl Coenzyme A / Q000235:genetics / Q000378:metabolism; D017209:Apoptosis / Q000235:genetics; D001483:Base Sequence; D001692:Biological Transport; D003066:Coenzyme A Ligases / Q000235:genetics / Q000378:metabolism*; D044943:Fatty Acid Desaturases / Q000235:genetics / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism; D017353:Gene Deletion; D015966:Gene Expression Regulation, Fungal; D006360:Heat-Shock Proteins / Q000378:metabolism; D000074923:High-Temperature Requirement A Serine Peptidase 2; D006706:Homeostasis / Q000502:physiology*; D050356:Lipid Metabolism / Q000502:physiology*; D024101:Mitochondrial Proteins; D008969:Molecular Sequence Data; D033903:Periplasmic Proteins / Q000378:metabolism; D025941:Protein Interaction Mapping; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000254:growth & development / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D012697:Serine Endopeptidases / Q000235:genetics / Q000378:metabolism*; D013230:Stearoyl-CoA Desaturase; D014280:Triglycerides / Q000378:metabolism; D020798:Two-Hybrid System Techniques
D000214:Acyl Coenzyme A; D005227:Fatty Acids; D006360:Heat-Shock Proteins; D024101:Mitochondrial Proteins; D033903:Periplasmic Proteins; D029701:Saccharomyces cerevisiae Proteins; D014280:Triglycerides; D044943:Fatty Acid Desaturases; D013230:Stearoyl-CoA Desaturase; C029627:delta-9 fatty acid desaturase; C061682:DegP protease; C511243:NMA111 protein, S cerevisiae; D012697:Serine Endopeptidases; D000074923:High-Temperature Requirement A Serine Peptidase 2; D003066:Coenzyme A Ligases; C511244:Faa1 protein, S cerevisiae; C090206:FAA4 protein, S cerevisiae