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

Dataset DOI: [10.5061/dryad.z34tmpgth](https://doi.org/10.5061/dryad.z34tmpgth)

## Description of the data and file structure

### File: PNAS_Data_Bankup.zip

**Description:** This folder contains all the data used for the figures in my submitted manuscript. The file names are organized according to the figure order, and within each file, subfolders are named according to the order of the panels, with the corresponding data provided.

### Figure 1

A. The raw data of western blot.

B. IF images showing co‐location of DRP1 and mitochondria (COX IV) in the myocardial tissue after CLP, n = 8 per group, scale bar = 25μm.

C. Activation level and quantification of DRP1 protein of myocardial tissue after CLP, n = 8 per group.

D. EM images showing mitochondria in the myocardial tissue of Sham, CLP, and CLP+Mdivi-1 (25mg/kg) group, n = 8 per grou..., ,