244: NEK7 couples SDHB to preserve mitochondrial electron transport and limit liver fibrosis

Sun Z et al., Nature Communications - Mitochondrial NEK7 is imported via MTS peptides, binds SDHB to stabilize complex II conformation, prevent reverse electron transport and ROS, and thereby protects against spontaneous and experimentally induced liver fibrosis. Key terms: NEK7, SDHB, reverse electron transport, ROS, liver fibrosis. Study Highlights:NEK7 localizes to hepatocyte mitochondria through two internal mitochondrial targeting signal peptides and co‑localizes with SDHB. NEK7 binds SDHB and stabilizes complex II spatial conformation without changing SDHB abundance or complex assembly. Hepatocyte NEK7 deficiency induces reverse electron transport, increases mitochondrial membrane potential and mtROS, suppresses respiration, and triggers spontaneous liver fibrosis while worsening CCl4‑induced fibrosis. RET inhibitors or NEK7 overexpression restore mitochondrial function and substantially attenuate CCl4‑ and CDAHFD‑induced liver fibrosis. Conclusion:NEK7 maintains respiratory chain electron transport homeostasis via SDHB binding and is a candidate therapeutic target to prevent or treat liver fibrosis Music:Enjoy the music based on this article at the end of the episode. Article title:NEK7 couples SDHB to orchestrate respiratory chain electron transport homeostasis that impedes liver fibrosis First author:Sun Z Journal:Nature Communications DOI:10.1038/s41467-025-65790-0 Reference:Sun Z., Le S., Hua H., Ren Y., Zhu W., Wang X., Gu W., Huang S., Zhong D., Sun Y., Zhang Y., Zhang A. & Jia Z. NEK7 couples SDHB to orchestrate respiratory chain electron transport homeostasis that impedes liver fibrosis. Nature Communications. 2025;16:10751. https://doi.org/10.1038/s41467-025-65790-0 License:CC BY 4.0 / Creative Commons Attribution 4.0 International License Support:Base by Base – Stripe donations: https://donate.stripe.com/7sY4gz71B2sN3RWac5gEg00 Official website https://basebybase.com On PaperCast Base by Base you’ll discover the latest in genomics, functional genomics, structural genomics, and proteomics. Episode link: https://basebybase.com/episodes/nek7-sdhb-mitochondria-fibrosis QC:This episode was checked against the original article PDF and publication metadata for the episode release published on 2025-12-30. QC Scope:- article metadata and core scientific claims from the narration- excludes analogies, intro/outro, and music- transcript coverage: Audited the spoken content for core mechanistic claims and experimental outcomes: mitochondrial localization of NEK7 via MTS, NEK7–SDHB binding and complex II stabilization, consequences of NEK7 deficiency (RET, mtROS, membrane potential, respiration), fibrosis phenotypes in hepatocyte NEK7 knockout mice, rescue by NEK- transcript topics: NEK7 mitochondrial localization and mitochondrial targeting sequences (MTS); NEK7–SDHB interaction and stabilization of mitochondrial complex II; NEK7 deficiency effects: RET, mtROS, membrane potential, respiration impairment; Spontaneous liver fibrosis in hepatocyte NEK7 knockout mice; NEK7 overexpression mitigates CCl4- and CDAHFD-induced liver fibrosis; RET inhibitors and ROS scavengers mitigate NEK7-deficiency–driven fibrosis QC Summary:- factual score: 10/10- metadata score: 10/10- supported core claims: 8- claims flagged for review: 0- metadata checks passed: 4- metadata issues found: 0 Metadata Audited:- article_doi- article_title- article_journal- license Factual Items Audited:- NEK7 localizes to mitochondria in hepatocytes via two mitochondrial targeting signal peptides (MTS).- NEK7 directly binds SDHB and stabilizes the spatial conformation of complex II, supporting forward electron transport.- NEK7 deficiency in hepatocytes i... Chapters (00:00:00) - How to prevent and treat liver scarring?(00:02:07) - Liver fibrosis: The mystery of NEK7(00:07:58) - Liver fibrosis: NeK7 protection(00:14:14) - Keep It Moving Forward