ArticleScience advances2020
DUSP6 SUMOylation protects cells from oxidative damage via direct regulation of Drp1 dephosphorylation.
Article in Science advances, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed.
- Magnetoreceptor Promotes Hepatocellular Carcinoma Development and Blunts Sorafenib-Induced Ferroptosis by Regulating Iron Homeostasis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Post-translational modifications of mitochondrion-related proteins: integrative orchestrators of cell fate networks in cardiovascular disease.Cell communication and signaling : CCS · 2026Review
- Bioactive Magnesium Silicate Activating Myocardial Energy Metabolism For Infarcted Myocardium Repair.Exploration (Beijing, China) · 2026Article
- Organelle regulation of SUMOylation: regulatory mechanisms and therapeutic application.Journal of advanced research · 2026Review
- LRRK2 G2019S mutation contributes to mitochondrial transfer dysfunction in a Drp1-STX17-dependent manner.Translational neurodegeneration · 2025Article
- N-terminal α-amino SUMOylation promotes phosphorylation-independent cofilin-1 translocation to the mitochondrial matrix and induces apoptosis.Nature communications · 2025Article
- SIRT3-Mediated Deacetylation of DRP1Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Mitochondrial fission - changing perspectives for future progress.Journal of cell science · 2025Review
- Deubiquitination of DNM1L by USP3 triggers the development and metastasis of gallbladder carcinoma.Biology direct · 2025Article
- Tufm lactylation regulates neuronal apoptosis by modulating mitophagy in traumatic brain injury.Cell death and differentiation · 2025Article
- Depleting chemoresponsive mitochondrial fission mediator DRP1 does not mitigate sarcoma resistance.Life science alliance · 2025Article
- DRP1: shedding light on the complex nexus of mitochondrial fission and breast cancer.Future oncology (London, England) · 2025Review
- Hypoxia Affects Mitochondrial Stress and Facilitates Tumor Metastasis of Colorectal Cancer Through Slug SUMOylation.Current molecular medicine · 2025Article
- SENP1-Mediated HSP90ab1 DeSUMOylation in Cardiomyocytes Prevents Myocardial Fibrosis by Paracrine Signaling.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Meldonium, as a potential neuroprotective agent, promotes neuronal survival by protecting mitochondria in cerebral ischemia-reperfusion injury.Journal of translational medicine · 2024Article
- SRF SUMOylation modulates smooth muscle phenotypic switch and vascular remodeling.Nature communications · 2024Article
- Sevoflurane augments neuroinflammation by regulating DUSP6 via YTHDF1 in postoperative cognitive dysfunction.Toxicology research · 2024Article
- MAP4K4 exacerbates cardiac microvascular injury in diabetes by facilitating S-nitrosylation modification of Drp1.Cardiovascular diabetology · 2024Article
- The role of mitochondrial dynamics and mitophagy in skeletal muscle atrophy: from molecular mechanisms to therapeutic insights.Cellular & molecular biology letters · 2024Review
- Cdk8/CDK19 promotes mitochondrial fission through Drp1 phosphorylation and can phenotypically suppress pink1 deficiency in Drosophila.Nature communications · 2024Article
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Authors and funding
13 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Imbalanced mitochondrial fission/fusion, a major cause of apoptotic cell death, often results from dysregulation of Drp1 phosphorylation of two serines, S616 and S637. Whereas kinases for Drp1-S616 phosphorylation are well-described, phosphatase(s) for its dephosphorylation remains unclear. Here, we show that dual-specificity phosphatase 6 (DUSP6) dephosphorylates Drp1-S616 independently of its known substrates ERK1/2. DUSP6 keeps Drp1-S616 phosphorylation levels low under normal conditions. The stability and catalytic function of DUSP6 are maintained through conjugation of small ubiquitin-like modifier-1 (SUMO1) and SUMO2/3 at lysine-234 (K234), which is disrupted during oxidation through transcriptional up-regulation of SUMO-deconjugating enzyme, SENP1, causing DUSP6 degradation by ubiquitin-proteasome. deSUMOylation underlies DUSP6 degradation, Drp1-S616 hyperphosphorylation, mitochondrial fragmentation, and apoptosis induced by H
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