ArticleCell research2014
A small natural molecule promotes mitochondrial fusion through inhibition of the deubiquitinase USP30.
Article in Cell research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 120 papers.
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Who cites it
120 citing papers in PubMed, 209 citations in OpenAlex.
- Balancing Ubiquitination and Deubiquitination in Apoptotic Protein Stability and Cancer Cell Survival.International journal of molecular sciences · 2026Review
- Decode the Ubiquitinome in Parkinson's Disease: From Pathological Aggregates to Targeted DUB Therapeutics.Neuroscience bulletin · 2026Review
- Mitochondrial dynamics in neurodevelopment and neurodevelopmental disorders.Nature reviews. Neuroscience · 2026Review
- Mitochondrial dynamics and cancer: mechanisms and targeted therapy.Cell biology and toxicology · 2026Review
- Targeting mitochondrial deubiquitinase USP30 to induce mitophagy in heteroplasmic mitochondrial diseases.Pharmacological reports : PR · 2026Article
- Targeting mitochondrial homeostasis as a cancer treatment strategy: current status and future prospects.Molecular cancer · 2026Review
- Mitophagy in the pathogenesis and management of disease.Cell research · 2026Review
- Research progress on mitochondria in bone defect repair: mechanisms and therapeutic implications.Frontiers in bioengineering and biotechnology · 2026Review
- Mitophagy in idiopathic pulmonary fibrosis: from molecular mechanisms to therapeutic opportunities.Frontiers in cell and developmental biology · 2026Review
- Mitochondrial fission and fusion in inflammatory diseases: mechanisms and therapeutic implications.Journal of translational medicine · 2025Review
- Targeting ubiquitination in disease and therapy.Signal transduction and targeted therapy · 2025Review
- Deubiquitinating enzymes in parkinson's disease: molecular mechanisms and therapeutic potential.Molecular medicine (Cambridge, Mass.) · 2025Review
- HSAInternational journal of molecular sciences · 2025Article
- Chimeric deubiquitinase engineering reveals structural basis for specific inhibition of the mitophagy regulator USP30.Nature structural & molecular biology · 2025Article
- Mitophagy's impacts on cancer and neurodegenerative diseases: implications for future therapies.Journal of hematology & oncology · 2025Review
- Role of mitochondria in physiological activities, diseases, and therapy.Molecular biomedicine · 2025Review
- Inhibition of USP30 Promotes Mitophagy by Regulating Ubiquitination of MFN2 by Parkin to Attenuate Early Brain Injury After SAH.Translational stroke research · 2025Article
- Structural Dynamics of the Ubiquitin Specific Protease USP30 in Complex with a Cyanopyrrolidine-Containing Covalent Inhibitor.Journal of proteome research · 2025Article
- Ubiquitin-Specific Protease Inhibitors for Cancer Therapy: Recent Advances and Future Prospects.Biomolecules · 2025Review
- The role of mitochondria-associated ER membranes in disease pathology: protein complex and therapeutic targets.Frontiers in cell and developmental biology · 2025Review
60 more citing papers are in PubMed but not listed here.
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Authors and funding
20 authors at 6 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mitochondrial fusion is a highly coordinated process that mixes and unifies the mitochondrial compartment for normal mitochondrial functions and mitochondrial DNA inheritance. Dysregulated mitochondrial fusion causes mitochondrial fragmentation, abnormal mitochondrial physiology and inheritance, and has been causally linked with a number of neuronal diseases. Here, we identified a diterpenoid derivative 15-oxospiramilactone (S3) that potently induced mitochondrial fusion to restore the mitochondrial network and oxidative respiration in cells that are deficient in either Mfn1 or Mfn2. A mitochondria-localized deubiquitinase USP30 is a target of S3. The inhibition of USP30 by S3 leads to an increase of non-degradative ubiquitination of Mfn1/2, which enhances Mfn1 and Mfn2 activity and promotes mitochondrial fusion. Thus, through the use of an inhibitor of USP30, our study uncovers an unconventional function of non-degradative ubiquitination of Mfns in promoting mitochondrial fusion.
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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.