Skip to main content
Journal cover image

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

Publication ,  Journal Article
Gu, X; Jouandin, P; Lalgudi, PV; Binari, R; Valenstein, ML; Reid, MA; Allen, AE; Kamitaki, N; Locasale, JW; Perrimon, N; Sabatini, DM
Published in: Nature
August 2022

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 deprivation2,3, 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 (SesnL431E) have reduced, leucine-insensitive mTORC1 activity. Notably, we find that flies can discriminate between food with or without leucine, and preferentially feed and lay progeny on leucine-containing food. This preference depends on Sestrin and its capacity to bind leucine. Leucine regulates mTORC1 activity in glial cells, and knockdown of Sesn in these cells reduces the ability of flies to detect leucine-free food. Thus, nutrient sensing by mTORC1 is necessary for flies not only to adapt to, but also to detect, a diet deficient in an essential nutrient.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

Nature

DOI

EISSN

1476-4687

Publication Date

August 2022

Volume

608

Issue

7921

Start / End Page

209 / 216

Location

England

Related Subject Headings

  • Signal Transduction
  • Sestrins
  • Neuroglia
  • Mutant Proteins
  • Mechanistic Target of Rapamycin Complex 1
  • Leucine
  • General Science & Technology
  • Food Preferences
  • Drosophila melanogaster
  • Drosophila Proteins
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Gu, X., Jouandin, P., Lalgudi, P. V., Binari, R., Valenstein, M. L., Reid, M. A., … Sabatini, D. M. (2022). Sestrin mediates detection of and adaptation to low-leucine diets in Drosophila. Nature, 608(7921), 209–216. https://doi.org/10.1038/s41586-022-04960-2
Gu, Xin, Patrick Jouandin, Pranav V. Lalgudi, Rich Binari, Max L. Valenstein, Michael A. Reid, Annamarie E. Allen, et al. “Sestrin mediates detection of and adaptation to low-leucine diets in Drosophila.Nature 608, no. 7921 (August 2022): 209–16. https://doi.org/10.1038/s41586-022-04960-2.
Gu X, Jouandin P, Lalgudi PV, Binari R, Valenstein ML, Reid MA, et al. Sestrin mediates detection of and adaptation to low-leucine diets in Drosophila. Nature. 2022 Aug;608(7921):209–16.
Gu, Xin, et al. “Sestrin mediates detection of and adaptation to low-leucine diets in Drosophila.Nature, vol. 608, no. 7921, Aug. 2022, pp. 209–16. Pubmed, doi:10.1038/s41586-022-04960-2.
Gu X, Jouandin P, Lalgudi PV, Binari R, Valenstein ML, Reid MA, Allen AE, Kamitaki N, Locasale JW, Perrimon N, Sabatini DM. Sestrin mediates detection of and adaptation to low-leucine diets in Drosophila. Nature. 2022 Aug;608(7921):209–216.
Journal cover image

Published In

Nature

DOI

EISSN

1476-4687

Publication Date

August 2022

Volume

608

Issue

7921

Start / End Page

209 / 216

Location

England

Related Subject Headings

  • Signal Transduction
  • Sestrins
  • Neuroglia
  • Mutant Proteins
  • Mechanistic Target of Rapamycin Complex 1
  • Leucine
  • General Science & Technology
  • Food Preferences
  • Drosophila melanogaster
  • Drosophila Proteins