AUTHOR=Liu Zhengyuan , Fang Danruo , Chen Kaijun , Dong Lingling , Huang Huaqiong , Chen Zhihua 

TITLE=Novel mitophagy inducer TJ0113 alleviates pulmonary inflammation during acute lung injury

JOURNAL=Frontiers in Pharmacology

VOLUME=Volume 16 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2025.1590458

DOI=10.3389/fphar.2025.1590458

ISSN=1663-9812

ABSTRACT=IntroductionAcute lung injury (ALI) is a severe respiratory disease with limited effective therapeutic options. Recent studies have highlighted mitochondrial damage as a crucial factor in the progression of ALI. Mitophagy, which facilitates the removal of damaged mitochondria, has been shown to reduce inflammation. Our collaborators constructed a small molecule mitophagy inducer, TJ0113. TJ0113 has received clinical approval for Alport syndrome from both the China National Medical Products Administration and the U.S. Food and Drug Administration. Therefore, we explored the potential of TJ0113 as a novel therapeutic for ALI.MethodsThe mitophagy-inducing potential of TJ0113 was assessed in HEK293T cells. The anti-inflammatory effects of TJ0113 were further evaluated in vivo using a mouse model of lipopolysaccharide (LPS)-induced ALI and in vitro using LPS-stimulated bone-marrow-derived macrophages (BMDMs).ResultsTJ0113 selectively induced mitophagy in damaged mitochondria. Furthermore, the PINK1–Parkin pathway was identified as a specific mitophagy pathway induced by TJ0113. In LPS-induced ALI mouse model, intraperitoneal injection of TJ0113 significantly reduced lung inflammation and mortality. In vitro, TJ0113 significantly inhibited the expression of LPS-induced inflammatory cytokines in BMDMs. Finally, we found that TJ0113 inhibited LPS-induced inflammation by inducing mitophagy and inhibiting nuclear factor κB (NF-κB) and inflammasome activation.ConclusionTJ0113 alleviates LPS-induced inflammation by inducing mitophagy and inhibiting NF-κB and inflammasome activation. Its selective action on damaged mitochondria suggests minimal side effects, positioning TJ0113 as a promising therapeutic candidate for ALI.