Macrophage SH3GLB1 is required for Rab7-1 mediated mitophagy in inflammation during acute lung injury

Acute lung injury (ALI) accompanied by an inflammatory response is an important complication after drowning. Macrophage activation and polarization are implicated in the inflammatory process of lipopolysaccharide (LPS)-induced ALI (LPS-ALI), but little is known about drowning-induced ALI (drowning-ALI). SH3GLB1 is a member of the endophilin family and has been shown to be involved in mitochondrial morphological changes and autophagy. However, its role in ALI remains unclear. Here,we performed single-cell profiling of lung immune cells isolated from the lungs of drowning-ALI mouse models. We found that the regulation of macrophages in drowning-ALI was similar to that in LPS-ALI. Specifically, SH3GLB1 was highly expressed in macrophages of drowning-ALI mouse models and was related to inflammation. Furthermore, SH3GLB1 deletion ameliorated LPS-ALI or drowning-ALI. In contrast, the restoration of SH3GLB1 expression provoked LPS-ALI and drowning-ALI. Mechanistically, SH3GLB1 was shown to interact with Rab7 to contribute to mitophagy, which resulted in mitochondrial dysfunction. Overall, these findings indicated that SH3GLB1 is required for Rab7-mediated mitophagy in inflammation during ALI and could be a novel target for lung protection.