NEK7 couples SDHB to orchestrate respiratory chain electron transport homeostasis that impedes liver fibrosis

Zhenzhen Sun, Le Sun, Hu Hua, Ying Ren, Wenping Zhu, Xu Wang, Wei Gu, Songming Huang, Dandan Zhong, Ying Sun (), Yue Zhang (), Aihua Zhang () and Zhanjun Jia ()
Additional contact information
Zhenzhen Sun: Guangzhou Road #72, Nanjing Key Laboratory of Pediatrics, Children’s Hospital of Nanjing Medical University
Le Sun: Guangzhou Road #72, Nanjing Key Laboratory of Pediatrics, Children’s Hospital of Nanjing Medical University
Hu Hua: Guangzhou Road #72, Nanjing Key Laboratory of Pediatrics, Children’s Hospital of Nanjing Medical University
Ying Ren: Guangzhou Road #72, Nanjing Key Laboratory of Pediatrics, Children’s Hospital of Nanjing Medical University
Wenping Zhu: Guangzhou Road #72, Nanjing Key Laboratory of Pediatrics, Children’s Hospital of Nanjing Medical University
Xu Wang: Guangzhou Road #72, Department of Endocrinology, Children’s Hospital of Nanjing Medical University
Wei Gu: Guangzhou Road #72, Department of Endocrinology, Children’s Hospital of Nanjing Medical University
Songming Huang: Guangzhou Road #72, Nanjing Key Laboratory of Pediatrics, Children’s Hospital of Nanjing Medical University
Dandan Zhong: Guangzhou Road #72, Nanjing Key Laboratory of Pediatrics, Children’s Hospital of Nanjing Medical University
Ying Sun: Guangzhou Road #72, Nanjing Key Laboratory of Pediatrics, Children’s Hospital of Nanjing Medical University
Yue Zhang: Guangzhou Road #72, Nanjing Key Laboratory of Pediatrics, Children’s Hospital of Nanjing Medical University
Aihua Zhang: Guangzhou Road #72, Nanjing Key Laboratory of Pediatrics, Children’s Hospital of Nanjing Medical University
Zhanjun Jia: Guangzhou Road #72, Nanjing Key Laboratory of Pediatrics, Children’s Hospital of Nanjing Medical University

Nature Communications, 2025, vol. 16, issue 1, 1-19

Abstract: Abstract The mode of electron transport in mitochondrial respiratory chain determines whether it generates energy or more reactive oxygen species (ROS), a key for cellular adaptation to diverse oxygen environments. However, the understanding of the mechanisms remains incomplete. Here, we find that NIMA-related kinase 7 (NEK7), targeted to mitochondria by its signal peptides, binds to succinate dehydrogenase complex iron sulfur subunit B (SDHB), stabilizing the spatial conformation of complex II and promoting forward electron transport. Deficiency of NEK7 in hepatocytes induces reverse electron transport (RET) and inhibits mitochondrial respiration, thereby promoting ROS generation, triggering spontaneous liver fibrosis and aggravating CCl4-induced liver fibrosis, which can be attenuated by RET inhibitors. More importantly, NEK7 overexpression effectively alleviates CCl4- and choline-deficient, high-fat diet-induced liver fibrosis. Overall, these findings highlight the pivotal role of NEK7 in orchestrating complex II and electron transport, providing new insights into the regulation of mitochondrial homeostasis and potential fibrosis treatments.

Date: 2025
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-025-65790-0 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-65790-0

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-025-65790-0

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().