Kidney Week

Abstract: FR-PO0357

Hypothermia Preserves Mitochondrial Oxidative Phosphorylation and Suppresses RNA Processing and Ribosome Biogenesis in Murine Ischemia-Reperfusion Injury (IRI)

Session Information

• AKI: Mechanisms - Metabolism and Repair
  October 23, 2026 | Location: Exhibit Hall A, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Acute Kidney Injury

• 103 AKI: Mechanisms

Authors

• Han, Suyeon, Daejeon Saint Mary's Hospital, Daejeon, Korea (the Republic of)

Suyeon Han, MD

• Chang, Yoon-Kyung, Daejeon Saint Mary's Hospital, Daejeon, Korea (the Republic of)

Yoon-Kyung Chang, MD, PhD

• Hwang, Yunkyeong, Daejeon Saint Mary's Hospital, Daejeon, Korea (the Republic of)

Yunkyeong Hwang, MD

• Park, Hwajin, Daejeon Saint Mary's Hospital, Daejeon, Korea (the Republic of)

Hwajin Park, MD

• Choi, Dae Eun, Chungnam National University Hospital, Daejeon, Korea (the Republic of)

Dae Eun Choi, MD, PhD

Background

Therapeutic hypothermia has demonstrated potent reno-protective effects in various experimental models; however, the underlying molecular mechanisms remain incompletely understood. We investigated the global transcriptional response to 32°C hypothermia in a murine IRI model.

Methods

Male C57BL/6 mice were assigned to sham, normothermic (37°C) IRI, or hypothermic (32°C) IRI groups (n=3 each), with hypothermia applied during ischemia. Kidneys were harvested 24 h after reperfusion for bulk RNA-seq, followed by DESeq2, GSEA (Hallmark/Reactome), and PPI analysis.

Results

A total of 7,972 DEGs were identified between normothermic IRI (N_IR) and sham. Hypothermia (32°C) induced 5,898 DEGs compared to N_IR (padj <= 0.05).
PPI analysis of upregulated DEGs revealed a mitochondrial oxidative phosphorylation module (NDUF, UQCR), with NDUF family genes as central hubs. GSEA confirmed strong enrichment of oxidative phosphorylation (NES = 2.06, padj = 1.9e-11), suggesting preserved mitochondrial function.
Conversely, GSEA and PPI analyses demonstrated coordinated suppression of RNA processing pathways, including mRNA splicing and nonsense-mediated decay, with Rnps1 as a key hub, along with downregulation of ribosome-related processes.

Conclusion

Hypothermia confers renoprotection by preserving mitochondrial oxidative phosphorylation while suppressing RNA processing and ribosome biogenesis, reflecting a shift toward energy conservation during ischemia–reperfusion injury.

Upregulated PPI module in hypothermic vs. normothermic IRI.

Downregulated PPI module in hypothermic vs. normothermic IRI.

Funding

• Government Support – Non-U.S.