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Updated: Jan 15, 2026
Inducing Acute Lung Injury in Mice by Direct Intratracheal Lipopolysaccharide Instillation
Published on: July 6, 2019
Onion-Mitochondria Inhibit Lipopolysaccharide-Induced Acute Lung Injury by Shaping Lung Macrophage Mitochondrial
Qingbo Xu1, Yun Teng2, Yinan Huang2
1Department of Microbiology and Immunology, University of Louisville, Louisville, KY, USA.
Abstract:
Mitochondrial dysfunction contributes to various inflammatory-related diseases by triggering the release of inflammatory molecules. Targeting mitochondrial dysfunction is emerging as a promising avenue for treating inflammatory diseases. Here, it is demonstrated that dietary plant-derived mitochondria (P-Mit) are capable of rescuing the lung macrophage mitochondrial (M-Mit) dysfunction in lipopolysaccharide (LPS)-induced mouse acute lung injury (ALI). Specifically, oral administration of dietary onion-derived mitochondria (O-Mit) can travel from the gut to the lungs in ALI mice, where preferentially uptake by lung macrophage mediated by the interaction between O-Mit phosphatic acid (PA) and macrophage complement C3b/C4b receptor 1 Like (CR1L), followed by fusing with murine M-Mit and by reprograming the M-Mit energy metabolism in the lungs of ALI mice. Further evidence suggests that O-Mit enriches methyl 3,4-dihydroxybenzoate (MDHB) inhibits M-Mit NADH dehydrogenase subunit 1 (ND1) gene expression in the epigenetic process, which represses LPS-induced complex I-related oxidative stress activation and excessive mitochondrial fission via modulating dynamin-related protein 1 (DRP1) phosphorylation and cardiolipin peroxidation in M-Mit, eventually rescues the LPS-induced ALI. Given LPS-induced 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-Mit.
Insights
Dietary plant mitochondria, specifically from onions, can rescue lung cell mitochondrial dysfunction in acute lung injury (ALI) models. This discovery offers a novel therapeutic strategy for treating inflammatory lung diseases like ALI.
Area of Science:
- Mitochondrial biology
- Immunology
- Gastroenterology
Background:
- Mitochondrial dysfunction is a key factor in inflammatory diseases.
- Targeting mitochondrial dysfunction presents a promising therapeutic approach.
- Acute lung injury (ALI) is often associated with mitochondrial dysfunction.
Purpose of the Study:
- To investigate the therapeutic potential of dietary plant-derived mitochondria (P-Mit) in rescuing lung macrophage mitochondrial dysfunction in a mouse model of ALI.
- To elucidate the mechanism by which P-Mit exert their protective effects in the lungs.
Main Methods:
- Oral administration of onion-derived mitochondria (O-Mit) to lipopolysaccharide (LPS)-induced ALI mice.
- Tracking O-Mit from the gut to the lungs and their uptake by lung macrophages.
- Analyzing O-Mit-macrophage interaction, fusion with lung mitochondria, and metabolic reprogramming.
- Investigating the role of methyl 3,4-dihydroxybenzoate (MDHB) in O-Mit and its epigenetic effects on mitochondrial gene expression (ND1).
- Assessing the modulation of oxidative stress, mitochondrial fission (DRP1 phosphorylation), and cardiolipin peroxidation.
Main Results:
- Dietary O-Mit successfully traveled from the gut to the lungs in ALI mice.
- O-Mit were preferentially taken up by lung macrophages via specific molecular interactions.
- O-Mit fused with lung macrophages' mitochondria, reprogramming their energy metabolism.
- O-Mit-derived MDHB epigenetically inhibited mitochondrial ND1 gene expression.
- This inhibition reduced oxidative stress and mitochondrial fission, ultimately rescuing LPS-induced ALI.
Conclusions:
- Dietary plant mitochondria, particularly O-Mit, can effectively treat mitochondrial dysfunction in lung macrophages during ALI.
- The therapeutic mechanism involves gut-lung trafficking, targeted uptake, mitochondrial fusion, and epigenetic modulation of mitochondrial function.
- Edible P-Mit represent a potential novel therapeutic strategy for human ALI and related inflammatory respiratory conditions.
