ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2025
SENP6 Maintains Mitochondrial Homeostasis by Regulating Mitochondrial Protein Import Through deSUMOylation of TOM40.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed.
- Mitochondrial quality control in health and disease: Updates 2026.Chinese medical journal · 2026Review
- The PPTC7/BNIP3/NIX axis induces cGAS/STING-mediated senescence and augments CAR-T efficacy by repressing tumor-intrinsic mitophagy.Journal of experimental & clinical cancer research : CR · 2026Article
- Study on the Role and Mechanism ofJournal of cardiovascular development and disease · 2026Article
- SENP6 Restrains NLRP3 Inflammasome Activation via DeSUMOylation-Driven K48-Linked Ubiquitination of NLRP3 in Acute Lung Injury.Research (Washington, D.C.) · 2026Article
- SENP6 Maintains Mitochondrial Homeostasis by Regulating Mitochondrial Protein Import Through deSUMOylation of TOM40.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
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Funding
Abstract
SUMOylation, a reversible post-translational modification, regulates various mitochondrial processes, including biogenesis, dynamics, mitophagy, and the mitochondrial unfolded protein response. Although SUMOylation is shown to be triggered by mitochondrial protein import failure in yeast, its impact on mammalian mitochondrial protein import remains unclear. Here, it is demonstrated that SENP6 knockdown-induced SUMOylation causes loss of mitochondrial proteostasis, which impairs mitochondrial morphology and function. Mechanistically, SENP6 knockdown dampens TOM complex assembly by SUMOylating TOM40, thereby hindering the mitochondrial protein import process, including TOM40 precursor, and ultimately disrupts mitochondrial homeostasis. Additionally, it is observed that CCCP treatment resulted in a decrease of SENP6 within mitochondria fraction, accompanied by increased TOM40 SUMOylation in the brains of 3×Tg-Alzheimer's disease (AD) mice or Aβ
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