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DCK (diquat)-induced lung injury

GSE244858 Mus musculus Expression profiling by high throughput sequencing 9 samples Submitted 2024/03/25 Platform GPL24247
Summary
Diquat (DQ) poisoning is a severe medical condition with life-threatening implications and multi-organ dysfunction, yet its underlying mechanism remains incompletely understood. This study unveils a critical process in DQ-induced toxicity. DQ disrupts the mitochondrial genome stability in endothelial cells, leading to the accumulation of Z-form DNA. This triggers an interaction between Z-DNA binding protein 1 (ZBP1) and receptor interacting protein kinase 3 (RIPK3), setting off RIPK3-dependent necroptotic and ferroptotic signaling pathways. Depletion of ZBP1 or RIPK3 in endothelial cells effectively inhibits both necroptosis and ferroptosis, reducing organ damage and mortality. Importantly, we discover that RIPK3 plays a dual role. It phosphorylates MLKL to induce necroptosis and phosphorylates FSP1, inhibiting its enzymatic activity and promoting ferroptosis. The phosphorylation of T163 in FSP1 is crucial for suppressing its activity. Combining the deletion of MLKL with vitamin K treatment proves highly effective in mitigating multi-organ damage and lethality caused by DQ.
Published in
Sensing of mitochondrial DNA by ZBP1 promotes RIPK3-mediated necroptosis and ferroptosis in response to diquat poisoning
Lai K, Wang J, Lin S et al. · Cell death and differentiation 2024 · PMID 38493248 · doi:10.1038/s41418-024-01279-5
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Direct links to NCBI, no account and no request form: the whole study as GSE244858_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 9 samples. Raw sequencing reads are also available from ENA.

Also filed as BioProject PRJNA1023733 and SRA study SRP464429. Searching any of these in the dataset finder brings you back here.

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