Sestrin mediates detection of and adaptation to low-leucine diets in Drosophila.

ABSTRACT: Mechanistic target of rapamycin complex 1 (mTORC1) regulates cell growth and metabolism in response to multiple nutrients, including the essential amino acid leucine¹. Recent work in cultured mammalian cells established the Sestrins as leucine-binding proteins that inhibit mTORC1 signalling during leucine deprivation^2,3, but their role in the organismal response to dietary leucine remains elusive. Here we find that Sestrin-null flies (Sesn^-/-) fail to inhibit mTORC1 or activate autophagy after acute leucine starvation and have impaired development and a shortened lifespan on a low-leucine diet. Knock-in flies expressing a leucine-binding-deficient Sestrin mutant (Sesn^L431E) have reduced, leucine-insensitive mTORC1 activity. Notably, we find that

SUBMITTER: Gu X 

PROVIDER: S-EPMC10112710 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature