Locally activated mitophagy contributes to a "built-in" protection against early burn-wound progression in rats.

Abstract Aims Deep burn-wounds undergo a dynamic progression in the initial or periburn area after insults, and the zone of stasis is considered as the crucial zone undergoing the deterioration, as well as a salvageable target. This study tries to explore a potential mitophagy-based “built-in” self-defense against this progression. Main methods A classic “comb” scald rat model was established. Histological and blood-flow observation were processed based on hematoxylin-eosin staining and laser analysis. Oxidative and apoptotic status were analyzed by commercial kits. Transmission-electron microscope, immunofluorescence staining, and western blot were applied to detect the mitophagy in the zone of stasis and potential regulators. Adenovirus-based gene-silence contributed to determine the role of HIF-1α as a regulatory mediator. Key findings We found that burn caused typical ischemia and histological deterioration in the zone of stasis, in parallel with increases in oxidative stress and apoptosis. Mitochondrial damage was involved in the aforementioned changes. Furthermore, we detected typical mitophagy in burn-wounds, which was contradictory to the burn-wound conversion. HIF-1α expression was closely related to the level of mitophagy, while BNIP3 and PARKIN are involved downstream. Significance We demonstrate that burn-induced mitochondrial impairment contributes to the mobilization of injurious mechanisms in the zone of stasis and that mitophagy provides a beneficial way to protect against burn-wound progression via the elimination of damaged mitochondria. Our findings offer insights into mitochondrial quality control in burn-wound progression and suggest the novel concept that HIF-1α may be a therapeutic target due to its possible regulatory effects on BNIP3- or PARKIN-mediated mitophagy.