Mitochondrial Double-Stranded RNA Triggers Ferroptosis via PKR-ISR Signaling in Renal Ischemia-Reperfusion Injury
Han, J.; Justin, R.; Criste, M. S.; Park, S.; Kusuma, F.; Lee, N.; Yang, Y.; Nguyen, K. A.; Park, S.; Kim, J.; Gil, H.-w.
Show abstract
Renal ischemia-reperfusion (IR) injury remains a leading cause of acute kidney injury, although the precise molecular pathways responsible for tissue injury are not fully understood. In this study, we demonstrate that IR initiates ferroptosis through activation of the PKR-dependent integrated stress response (ISR), which is driven by the accumulation of mitochondrial double-stranded RNA (dsRNA). Our mechanistic investigations reveal that IR perturbs mitochondrial homeostasis, leading to the accumulation of mitochondrial dsRNA and its subsequent release into the cytosol, thereby activating the dsRNA-dependent kinase PKR. Activation of PKR results in eIF2 phosphorylation and maladaptive ISR signaling, which facilitates ferroptosis and impairs renal function. Notably, genetic ablation of PKR or pharmacological intervention to inhibit ISR significantly reduced ferroptosis and preserved renal function. Collectively, these results identify the mitochondrial dsRNA-PKR-ISR axis as a critical mediator of ferroptotic renal injury and highlight its potential as a therapeutic target in ischemic acute kidney injury.
Matching journals
The top 7 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Single-cell profiling of healthy human kidney reveals features of sex-based transcriptional programs and tissue-specific immunity 96%
- Defining cellular complexity in human autosomal dominant polycystic kidney disease by multimodal single cell analysis 96%
- Single cell transcriptional and chromatin accessibility profiling redefine cellular heterogeneity in the adult human kidney 95%
Similar papers in this journal
Similar papers in this journal
Similar papers in this journal
- Endothelial Prolyl Hydroxylase 3 Mitigates Maladaptive Inflammation to Promote Post-Ischemic Kidney Repair 95%
- Enhancer and super-enhancer landscape in polycystic kidney disease 94%
- Dynamic Single Cell Transcriptomics Defines Kidney FGF23/KL Bioactivity and Novel Segment-Specific Inflammatory Targets 94%
Similar papers in this journal
- Non-canonical hepatic androgen receptor mediates glucagon sensitivity in female mice through the PGC1α/ERRα/mitochondria axis 93%
- Recruitment of BAG2 to DNAJ-PKAc scaffolds promotes cell survival and resistance to drug-induced apoptosis in fibrolamellar carcinoma 92%
- SF3B1 promotes tumor malignancy through splicing-independent co-activation of HIF1α 92%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.