Mitochondrial citrate accumulation triggers senescence of alveolar epithelial cells contributing to pulmonary fibrosis in mice.

ABSTRACT: Alveolar epithelial cell (AEC) senescence is implicated in the pathogenesis of pulmonary fibrosis (PF). However, the exact mechanism underlying AEC senescence during PF remains poorly understood. Here, we reported an unrecognized mechanism for AEC senescence during PF. We found that, in bleomycin (BLM)-induced PF mice, the expressions of isocitrate dehydrogenase 3α (Idh3α) and citrate carrier (CIC) were significantly down-regulated in the lungs, which could result in mitochondria citrate (citrate^mt) accumulation in our previous study. Notably, the down-regulation of Idh3α and CIC was related to senescence. The mice with AECs-specific Idh3α and CIC deficiency by adenoviral vector exhibited spontaneous PF and senescence in the lungs. In vitro, co-inhibition of Idh3α and CIC

SUBMITTER: Hong JR 

PROVIDER: S-EPMC10320039 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature