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Enhanced mitophagy promotes lung repair and regeneration by restoring epithelial metabolic fitness [AT2s RNA-Seq]

GSE317253 Mus musculus Expression profiling by high throughput sequencing 8 samples Submitted 2026/02/26 Platform GPL24247
Summary
Alveolar Type II cells (AT2s) are the stem cells in the alveoli, responsible for both alveolar homeostasis and regeneration. Mitochondrial dysfunction has been reported in the AT2 cells from both chronic and acute injury induced alveolar diseases, including idiopathic pulmonary fibrosis (IPF) and viral pneumonia. Here, we demonstrate that genetic depletion of Ubiquitin Specific Peptidase 30 (USP30), a negative regulator of mitophagy, boosts mitophagy and restores mitochondrial function, leading to protection from injury induced AT2 apoptosis and increased AT2 stem cell activity. Both global Usp30 knockout (KO) and AT2-specific Usp30 KO protects the mice from bleomycin induced lung fibrosis and influenza puneumonia. Moreover, pharmaceutical inhibition of USP30 using a small molecule inhibitor effectively alleviates lung fibrosis and influenza pneumonia. Our study underscores a therapeutic potiential of USP30 inhibition for the treatment of injury induced alveolar diseases, offering a promising strategy for treating injury induced diseases
Published in
Mitophagy promotes lung repair and regeneration by restoring epithelial metabolic fitness
Wu P, Chen J, Liu L et al. · Nature communications 2026 · PMID 41980941 · doi:10.1038/s41467-026-71728-x
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Also filed as BioProject PRJNA1406626 and SRA study SRP665546. Searching any of these in the dataset finder brings you back here.

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