ArticleNature structural & molecular biology2017
Mechanism and regulation of the Lys6-selective deubiquitinase USP30.
Article in Nature structural & molecular biology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 124 papers.
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Who cites it
124 citing papers in PubMed, 219 citations in OpenAlex.
- Pathological Mechanisms and Therapeutic Potential of Mitochondrial Dysfunction in Heart Failure.Reviews in cardiovascular medicine · 2026Review
- ZnF-UBP domains regulate deubiquitinase activity by relieving ubiquitin product inhibition.Nature communications · 2026Article
- Substrate biasing in UCHL5 proteoforms.bioRxiv : the preprint server for biology · 2026Article
- Global analysis of cancer cell responses to USP9X inhibition.The EMBO journal · 2026Article
- Reprogramming of bacterial virulence by lysine acetylation.Nature communications · 2026Article
- Phosphorylated ubiquitin is a secondary messenger and an epigenetic mark mediating mitochondria to nucleus signaling.bioRxiv : the preprint server for biology · 2026Article
- Mitophagy promotes lung repair and regeneration by restoring epithelial metabolic fitness.Nature communications · 2026Article
- The Metabolic Role of Mitochondria in the Perinatal Cardiac Development and Cardiovascular Diseases.Exploration (Beijing, China) · 2026Review
- USP30-mediated Deubiquitination of Hexokinase 2 controls the metabolic fate of glucose and tumor progression.Cell death & disease · 2026Article
- USP25 inhibition ameliorates Parkinson's disease by restoring mitophagy.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Mastering cardiomyocyte mitophagy: molecular governance, pathological derailment and therapeutics.PeerJ · 2026Review
- mTORC1-USP30-LEF1 Cascade Regulates Cancer Stemness and Malignant Progression Through Mitonuclear Crosstalk.MedComm · 2025Article
- Mitochondrial Quality Control in Neurodegeneration and Cancer: A Common Denominator, Distinct Therapeutic Challenges.International journal of molecular sciences · 2025Review
- Chimeric deubiquitinase engineering reveals structural basis for specific inhibition of the mitophagy regulator USP30.Nature structural & molecular biology · 2025Article
- Mitophagy mitigates mitochondrial fatty acid β-oxidation deficient cardiomyopathy.Nature communications · 2025Article
- Targeting mitophagy in neurodegenerative diseases.Nature reviews. Drug discovery · 2025Review
- Structural Dynamics of the Ubiquitin Specific Protease USP30 in Complex with a Cyanopyrrolidine-Containing Covalent Inhibitor.Journal of proteome research · 2025Article
- Expression and role of deubiquitinating enzymes in thyroid carcinoma.Briefings in functional genomics · 2025Review
- Research progress of deubiquitinating enzymes in cerebral ischemia-reperfusion injury.Frontiers in aging neuroscience · 2025Review
- The emerging roles of ubiquitin-like modifications in regulating HIV replication and host defense.Frontiers in cellular and infection microbiology · 2025Review
64 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Damaged mitochondria undergo mitophagy, a specialized form of autophagy that is initiated by the protein kinase PINK1 and the ubiquitin E3 ligase Parkin. Ubiquitin-specific protease USP30 antagonizes Parkin-mediated ubiquitination events on mitochondria and is a key negative regulator of mitophagy. Parkin and USP30 both show a preference for assembly or disassembly, respectively, of Lys6-linked polyubiquitin, a chain type that has not been well studied. Here we report crystal structures of human USP30 bound to monoubiquitin and Lys6-linked diubiquitin, which explain how USP30 achieves Lys6-linkage preference through unique ubiquitin binding interfaces. We assess the interplay between USP30, PINK1 and Parkin and show that distally phosphorylated ubiquitin chains impair USP30 activity. Lys6-linkage-specific affimers identify numerous mitochondrial substrates for this modification, and we show that USP30 regulates Lys6-polyubiquitinated TOM20. Our work provides insights into the architecture, activity and regulation of USP30, which will aid drug design against this and related enzymes.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.