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

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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.

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Acknowledgements

The authors thank Drs. Michael Fasullo, Steven Hanes, and Randall Morse for helpful discussions and comments on the manuscript. This work was supported by grants from the American Heart Association (AHA 0151215T to CCD and AHA 0315294T, a pre-doctoral fellowship, to FT) and the National Inst6itutes of Health (GM56850 to PNB and CCD).

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Authors and Affiliations

  1. Center for Metabolic Disease, Ordway Research Institute, Inc., 150 New Scotland Avenue, Albany, NY, 12208-3425, USA

    Fumin Tong, Paul N. Black, Lori Bivins, Steven Quackenbush & Concetta C. DiRusso

  2. Center for Cardiovascular Sciences, Albany Medical College, 150 New Scotland Avenue, Albany, NY, 12208-3425, USA

    Fumin Tong, Paul N. Black, Lori Bivins, Steven Quackenbush & Concetta C. DiRusso

  3. Department of Tropical Medicine, Charles University, Prague, Czech Republic

    Vlasta Ctrnacta

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  1. Fumin Tong
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  6. Concetta C. DiRusso
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Correspondence to Concetta C. DiRusso.

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Communicated by S. Hohmann

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Tong, F., Black, P.N., Bivins, L. et al. Direct interaction of Saccharomyces cerevisiae Faa1p with the Omi/HtrA protease orthologue Ynm3p alters lipid homeostasis. Mol Genet Genomics 275, 330–343 (2006). https://doi.org/10.1007/s00438-005-0089-1

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  • DOI: https://doi.org/10.1007/s00438-005-0089-1

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