Fig. 6.

Schematic depicting the protective mechanism of selonsertib against mitochondrial damage. In LPS/GalN-induced ALF, excessive ASK1 phosphorylation induces JNK-mediated DRP1 activation and mitochondrial translocation in macrophages, which in turn promotes excessive mitochondrial fission. Enhanced mitochondrial fragmentation then leads to mitochondrial damage, an increase in mitochondrial oxidative stress, and the overproduction of inflammatory cytokines by macrophages. Selonsertib, a selective inhibitor of ASK1, protects against ALF by re-establishing the mitochondrial fusion-fission balance through suppressing the ASK1–JNK–DRP1 pathway in macrophages, rescuing mitochondrial damage and relieving inflammatory injury