Sirt3 restricts tumor initiation via promoting LONP1 deacetylation and K63 ubiquitination.

ABSTRACT:

Background

Sirtuin 3 (Sirt3) is a controversial regulator of carcinogenesis. It residents in the mitochondria and gradually decays during aging. In this study, we tried to investigate the role of Sirt3 in carcinogenesis and to explore its involvement in metabolic alteration.

Methods

We generated conditional intestinal epithelium Sirt3-knockout mice by crossing Apc^Min/+; Villin-Cre with Sirt3^fl/fl (AVS) mice. The deacetylation site of Lon protease-1 (LONP1) was identified with Mass spectrometry. The metabolic flux phenotype was determined by Seahorse bioanalyzer.

Results

We found that intestinal epithelial cell-specific ablation of Sirt3 promotes primary tumor growth via stabilizing mitochondrial LONP1. Notably, we newly identified that Sirt3 deac

SUBMITTER: Wu L 

PROVIDER: S-EPMC9899405 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature