Physiology: An atypical switch for metabolism and ageing

Abstract

The enzyme S6K1 enzyme phosphorylates the enzyme glutamyl-prolyl t-RNA synthetase to modulate metabolic activity and lifespan, revealing an atypical role for this synthetase as a target of a key metabolic signalling pathway.

Figure 1. A phosphorylation switch alters lipid uptake and longevity.

a, As part of a large protein complex, the protein mTOR can activate the kinase enzyme S6K1. Arif et al. report that S6K1 phosphorylates (P) the protein glutamyl-prolyl t-RNA synthetase (EPRS) on the amino-acid residue Serine 999 (Ser⁹⁹⁹). This switch promotes interaction with the fatty-acid transporter protein FATP1, leading to increased lipid uptake into fat tissue. b, If Ser⁹⁹⁹ is mutated to the amino-acid residue alanine in mice, such that it cannot be phosphorylated, the interaction with FATP1 does not occur — these animals have lower fat mass and live longer than controls.