Data from: Microvesicle release drive cycles of mitophagy flux disruption and inflammatory amplification in sepsis-induced myocardial dysfunction

Sepsis-induced myocardial dysfunction strongly contributes to high
mortality in patients with sepsis by exacerbating systemic organ failure;
however, the onset and molecular mechanisms driving this vicious cycle
remain unclear. Here, we revealed that DRP1-mediated mitochondrial fission
and excessive reactive oxygen species accumulation are central to
disrupting mitophagy flux and triggering inflammatory cascades. Using
cecal ligation and puncture mice and lipopolysaccharide-treated HL-1 cell
models, combined with advanced imaging and molecular analyses, we
demonstrated that elevated reactive oxygen species activates the RIP1/RIP3
pathway, impairing mitophagy flux and promoting the release of
microvesicles containing mitochondrial inner membrane components and
mitochondrial DNA. These microvesicles amplify inflammatory responses
through the cGAS-STING and RIP1/RIP3 pathways, driving the production of
damage- and pathogen-associated molecular patterns. This study highlights
two interlinked vicious cycles, mitophagy flux disruption and damage- and
pathogen-associated molecular pattern amplification, as critical drivers
of sepsis-induced myocardial injury, providing novel therapeutic targets
for mitigating inflammatory damage and improving clinical outcomes in
patients with sepsis.