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TORC1 regulates Pah1 phosphatidate phosphatase activity via the Nem1/Spo7 protein phosphatase complex

Emmanuelle Dubots1, Stéphanie Cottier1, Marie-Pierre Péli-Gulli1

  • 1Department of Biology, University of Fribourg, CH-1700 Fribourg, Switzerland.

Plos One
|August 14, 2014
PubMed

Insights

The target of rapamycin complex 1 (TORC1) pathway inhibits lipid synthesis by regulating the phosphatidate phosphatase Pah1. This study reveals a new TORC1 signaling branch controlling lipin function, potentially conserved in humans.

Area of Science:

  • Cellular biology
  • Molecular biology
  • Metabolic regulation

Background:

  • The target of rapamycin complex 1 (TORC1) is a conserved kinase regulating cell growth and metabolism.
  • TORC1 deregulation is linked to diseases like cancer, type 2 diabetes, and obesity.
  • Lipin proteins, like yeast Pah1, are key regulators of lipid metabolism, influencing triacylglycerol synthesis.

Purpose of the Study:

  • To investigate the role of yeast TORC1 in regulating lipid metabolism, specifically triacylglycerol accumulation.
  • To identify the mechanisms by which TORC1 controls the activity of the lipin Pah1.
  • To explore a potential conserved signaling pathway involving TORC1 and lipin regulation.

Main Methods:

  • Yeast genetics and molecular biology techniques.
  • Phosphorylation assays to assess enzyme activity.
  • Analysis of triacylglycerol levels in yeast strains.

Main Results:

  • Yeast TORC1 directly and indirectly inhibits the function of the lipin Pah1.
  • TORC1 regulates Pah1 activity, in part, by controlling the phosphorylation of Nem1 within the Nem1-Spo7 complex.
  • This regulation prevents the excessive accumulation of triacylglycerol in yeast cells.

Conclusions:

  • A novel TORC1 effector pathway controlling lipin function in yeast has been identified.
  • This pathway involves the regulation of the Nem1-Spo7 protein phosphatase module.
  • The findings suggest a conserved mechanism for TORC1-mediated lipid metabolism control, with implications for human health.

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