SIRT3 regulates PDHA1 acetylation in HUVECs to modulate inflammation and pyroptosis under clinorotation.

ABSTRACT: Microgravity-induced endothelial inflammation contributes to cardiovascular dysfunction in astronauts, but the metabolic mechanisms involved are not fully defined. Sirtuin-3 (SIRT3), a mitochondrial deacetylase, regulates cellular metabolism and redox balance. The results demonstrate that two-dimensional clinorotation-induced simulated microgravity suppresses SIRT3 in human umbilical vein endothelial cells (HUVECs), resulting in mitochondrial dysfunction, NLRP3 inflammasome activation, and pyroptosis. SIRT3 overexpression mitigated these effects, while SIRT3 knockdown exacerbated them. Mechanistically, SIRT3 deletion promoted acetylation of pyruvate dehydrogenase E1α (PDHA1) at lysine 83, inhibiting pyruvate dehydrogenase complex (PDHC) activity and shifting metabolism toward higher levels

SUBMITTER: Jiang M 

PROVIDER: S-EPMC12663655 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature