
SIRT2はアミノ酸欠乏などの栄養ストレス下でACSS2のK271を脱アセチル化し、その後の分解を促進することで脂肪合成を抑制する。


coremsg

De novo lipogenesis is associated with the development of human diseases such as cancer, diabetes, and obesity. At the core of lipogenesis lies acetyl coenzyme A (CoA), a metabolite that plays a crucial role in fatty acid synthesis. One of the pathways contributing to the production of cytosolic acetyl-CoA is mediated by acetyl-CoA synthetase 2 (ACSS2). Here, we reveal that when cells encounter nutrient stress, particularly a deficiency in amino acids, Sirtuin 2 (SIRT2) catalyzes the deacetylation of ACSS2 at the lysine residue K271. This results in K271 ubiquitination and subsequently proteasomal degradation of ACSS2. Substitution of K271 leads to decreased ubiquitination of ACSS2, increased ACSS2 protein level, and thus increased lipogenesis. Our study uncovers a mechanism that cells employ to efficiently manage lipogenesis during periods of nutrient stress.

### Competing Interest Statement

HL is a founder and consultant for Sedec Therapeutics

SIRT2-Mediated ACSS2 K271 Deacetylation Suppresses Lipogenesis Under Nutrient Stress

栄養ストレス下でsirt2がacss2のk271脱アセチル化を介して脂肪合成を抑制する


栄養ストレス下でSIRT2がACSS2のK271脱アセチル化を介して脂肪合成を抑制する
