Onion-Mitochondria Inhibit Lipopolysaccharide-Induced Acute Lung Injury by Shaping Lung Macrophage Mitochondrial Function.

Summary

In LPS-induced ALI mice, orally delivered onion-derived mitochondria trafficked to lungs, were preferentially taken up by macrophages via PA–CR1L interaction, fused with host mitochondria, and reprogrammed bioenergetics. MDHB-enriched O-Mit epigenetically suppressed ND1, dampened complex I-driven oxidative stress, limited DRP1-mediated fission and cardiolipin peroxidation, and ameliorated lung injury.

Key Findings

• Oral onion-derived mitochondria trafficked from gut to lung and were preferentially taken up by lung macrophages via PA–CR1L interaction.
• O-Mit fused with host macrophage mitochondria and reprogrammed energy metabolism to counter LPS-induced dysfunction.
• MDHB-enriched O-Mit epigenetically suppressed ND1, reducing complex I-driven oxidative stress, DRP1-mediated fission, and cardiolipin peroxidation, thereby rescuing LPS-induced ALI.

Clinical Implications

Although preclinical, ingestible plant-derived mitochondria could form the basis of safe, noninvasive immunometabolic therapies for ALI/ARDS by restoring macrophage mitochondrial function. Translation will require rigorous safety, biodistribution, and efficacy studies in large animals and humans.

Limitations

• Mouse LPS-ALI model may not fully recapitulate human ALI/ARDS pathobiology
• Safety, immunogenicity, and dose scaling of plant-derived mitochondria in humans remain untested

Future Directions

Quantify biodistribution and persistence, assess immunogenicity and safety in large animals, validate efficacy across diverse ALI/ARDS models, and explore receptor/ligand specificity (PA–CR1L) in human macrophages.