Phosphatidic acid and lipid-sensing by mTOR

Mammalian target of rapamycin (mTOR) has been implicated as a sensor of nutrient sufficiency for dividing cells and is activated by essential amino acids and glucose. However, cells also require lipids for membrane biosynthesis. A central metabolite in the synthesis of membrane phospholipids is phosphatidic acid (PA), which is required for the stability and activity of mTOR complexes. Although PA is commonly generated by the phospholipase D-catalyzed hydrolysis of phosphatidylcholine, PA is also generated by diacylglycerol kinases and lysophosphatidic acid acyltransferases, which are at the center of phospholipid biosynthesis. It is proposed that the responsiveness of mTOR/TOR to PA evolved as a means for sensing lipid precursors for membrane biosynthesis prior to doubling the mass of a cell and dividing.

► Phosphatidic acid (PA) is a central metabolite in membrane biosynthesis.
► TOR/mTOR is a sensor of amino acids and the glucose needed for cell growth.
► PA is a critical regulator of mTOR, and likely more primitive TOR species also.
► The PA requirement for TOR may represent a means for the sensing of lipids, which are also required for cell growth.