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Targeting mitochondrial dysfunction is emerging as a promising avenue for treating inflammatory diseases. Here, it is demonstrated that dietary plant\u2010derived mitochondria (P\u2010Mit) are capable of rescuing the lung macrophage mitochondrial (M\u2010Mit) dysfunction in lipopolysaccharide (LPS)\u2010induced mouse acute lung injury (ALI). Specifically, oral administration of dietary onion\u2010derived mitochondria (O\u2010Mit) can travel from the gut to the lungs in ALI mice, where preferentially uptake by lung macrophage mediated by the interaction between O\u2010Mit phosphatic acid (PA) and macrophage complement C3b\/C4b receptor 1 Like (CR1L), followed by fusing with murine M\u2010Mit and by reprograming the M\u2010Mit energy metabolism in the lungs of ALI mice. Further evidence suggests that O\u2010Mit enriches methyl 3,4\u2010dihydroxybenzoate (MDHB) inhibits M\u2010Mit NADH dehydrogenase subunit 1 (ND1) gene expression in the epigenetic process, which represses LPS\u2010induced complex I\u2010related oxidative stress activation and excessive mitochondrial fission via modulating dynamin\u2010related protein 1 (DRP1) phosphorylation and cardiolipin peroxidation in M\u2010Mit, eventually rescues the LPS\u2010induced ALI. Given LPS\u2010induced mouse model of ALI is widely used to study human ALI and acute respiratory distress syndrome, this finding provides a clinical potential for the treatment of human ALI via edible P\u2010Mit.<\/jats:p>","DOI":"10.1002\/advs.202506107","type":"journal-article","created":{"date-parts":[[2025,10,6]],"date-time":"2025-10-06T23:40:22Z","timestamp":1759794022000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Onion\u2010Mitochondria Inhibit Lipopolysaccharide\u2010Induced Acute Lung Injury by Shaping Lung Macrophage Mitochondrial Function"],"prefix":"10.1002","volume":"12","author":[{"given":"Qingbo","family":"Xu","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology University of Louisville  Louisville KY 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