CGAS-STING-NF-κB Axis Mediates Rotenone-Induced NLRP3 Inflammasome Activation Through Mitochondrial DNA Release.

ABSTRACT: Rotenone, a classical inhibitor of mitochondrial complex I, disrupts electron transport and promotes the generation of reactive oxygen species (ROS), contributing to inflammation and cell death. However, the precise molecular mechanisms linking mitochondrial dysfunction to inflammatory signaling remain incompletely understood. In this study, we investigated the role of the cGAS-STING pathway in rotenone-induced NLRP3 inflammasome activation in PMA-differentiated THP-1 macrophages. Rotenone treatment activated the cGAS-STING axis, as evidenced by increased cGAS expression and the phosphorylation of STING and TBK1. This activation led to the nuclear translocation of NF-κB and the upregulation of NLRP3, promoting inflammasome priming and IL-1β secretion. Inhibition of STING using H-151 marked

SUBMITTER: Mun Y 

PROVIDER: S-EPMC12649239 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature