Abstract: FR-PO0358
Targeted E3 Ubiquitin Ligase MAP3K1-Induced Mitophagy Alleviates AKI
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
- Lin, Ting, Guangdong Provincial People's Hospital, Guang zhou, Guangdong, China
- Qin, Lele, Guangdong Provincial People's Hospital, Guang zhou, Guangdong, China
- Ye, Zhiming, Guangdong Provincial People's Hospital, Guang zhou, Guangdong, China
Background
IRI-induced AKI involves mitochondrial dysfunction and tubular epithelial injury. Mitophagy preserves mitochondrial homeostasis, partly through E3 ligase-mediated ubiquitination. MAP3K1 contains both kinase and E3 ligase domains, but its renal role remains unclear. Preliminary data showed dynamic MAP3K1 expression and mitochondrial enrichment during AKI, while MAP3K1 knockdown aggravated mitochondrial injury. This study explored MAP3K1-mediated mitophagy in IRI-AKI.
Methods
Single-cell RNA-seq identified dynamic MAP3K1 changes in adaptive PT cells. Its expression and mitochondrial localization were validated in AKI models, and MEC1-mediated MAP3K1 recruitment was assessed in vivo and in vitro.
Results
MAP3K1 decreased during IRI injury but recovered during repair. MEC1 promoted MAP3K1–TSPO proximity, reduced renal and mitochondrial injury, and enhanced K63-linked ubiquitination- and p62-dependent mitophagy.
Conclusion
MAP3K1 regulates mitochondrial quality control in IRI-induced AKI. Its targeted recruitment to mitochondrial TSPO attenuates renal injury by enhancing K63-linked ubiquitination- and p62-dependent mitophagy.
H/R promoted MAP3K1 recruitment to mitochondrial TSPO; MAP3K1 knockdown worsened mitochondrial injury.
MEC1 dose-dependently recruited MAP3K1 to mitochondria and alleviated IRI-AKI