2. Academic Validation
  3. Selenoprotein H targets MTCH2 to regulate MFN2-dependent mitochondrial quality control to alleviate acute kidney injury

Selenoprotein H targets MTCH2 to regulate MFN2-dependent mitochondrial quality control to alleviate acute kidney injury

  • J Adv Res. 2025 Nov 26:S2090-1232(25)00955-5. doi: 10.1016/j.jare.2025.11.059.
Dongliu Luo 1,  Yaning Qiu 2,  Jiahong Chu 2,  Haodong Hu 2,  Yanhe Zhang 2,  Yu Xia 3,  Fuze She 2,  Shiwen Xu 2,  Fating Zhu 4,  Zhiruo Miao 5,  Shu Li 6
Affiliations

Affiliations

  • 1 College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, China; College of Animal Science and Technology, Henan University of Science and Technology, Luoyang 471023, China.
  • 2 College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, China.
  • 3 College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, China; Animal Science College, Hebei North University, Zhangjiakou 075000, China.
  • 4 National Selenium-Rich Product Quality Supervision and Inspection Center, Enshi 445000, China.
  • 5 College of Animal Science and Technology, Northeast Agricultural University, Harbin 150030, China. Electronic address: [email protected].
  • 6 College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, China. Electronic address: [email protected].
PMID: 41314281 DOI: 10.1016/j.jare.2025.11.059
Abstract

Introduction: Mitochondrial dysfunction is recognized as a pivotal event in the pathogenesis of acute kidney injury (AKI). Selenoprotein (SelH), a mammalian selenoprotein, is extensively involved in regulating of diseases associated with mitochondrial dysfunction. However, its regulatory role in mitochondrial quality control during AKI remains unclear.

Objectives: This study aims to explore the impact of SelH on AKI and potential regulatory mechanisms of SelH in AKI.

Methods: In vivo, a cisplatin (CP)-induced AKI model was established using SelH knockout mice to evaluate renal injury. Additionally, co-immunoprecipitation (Co-IP). combined with mass spectrometry, Co-IP assays, laser confocal microscopy, and molecular docking were employed to identify proteins interacting with SelH. In vitro, SelH/mitochondrial carrier homolog 2 (MTCH2) knockdown and overexpression models were constructed in HEK293t cells. Indicators related to oxidative stress, mitochondrial biogenesis, mitochondrial dynamics, Mitophagy, and Apoptosis were analyzed.

Results: MTCH2 was identified as a potential interacting partner of SelH. Deficiency of renal SelH directly triggered oxidative stress, impaired mitochondrial biogenesis, disrupted mitochondrial dynamics, enhanced Mitophagy, and promoted Apoptosis. In HEK293t cells, SelH targeted MTCH2 to regulate mitofusin 2 (MFN2), thereby promoting mitochondrial fusion, alleviating mitochondrial dysfunction, maintaining mitochondrial quality control (MQC) homeostasis, and reducing renal oxidative damage and Apoptosis.

Conclusion: The results showed that SelH targets the MTCH2/MFN2 aixs to maintain MQC balance, alleviate oxidative stress and cell Apoptosis induced by AKI. This study not only supplements kidney specific regulatory targets for the field of mitochondrial medicine but also suggests that SelH could serve as a potential molecule for proactive medicine intervention in AKI, providing experimental evidence for the early intervention of AKI.

Keywords

Acute kidney injury; Apoptosis; MTCH2; Restored mitochondrial homeostasis and functionality; Selenoprotein H.

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