ArticleeLife2020
Skd3 (human ClpB) is a potent mitochondrial protein disaggregase that is inactivated by 3-methylglutaconic aciduria-linked mutations.
Article in eLife, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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Who cites it
49 citing papers in PubMed, 73 citations in OpenAlex.
- Paradoxical non-catalytic kinase functions are driven by inhibitor-induced displacement of autoinhibitory domains.Molecular systems biology · 2026Article
- HAX1 drives assembly and activation of the mitochondrial intermembrane space chaperone CLPB.bioRxiv : the preprint server for biology · 2026Article
- Hypoxia rescues complex 1-associated disease caused by proteostatic defects.Nature metabolism · 2026Article
- MICU proteins facilitate calcium-dependent mitochondrial metabolon formation to regulate cellular energetics independently of MCU.Nature metabolism · 2026Article
- Neuronal mitochondrial disaggregase CLPB ameliorates Huntington's disease pathology in mice.Theranostics · 2026Article
- CircPAFAH1B2 induces chondrocytes mitochondrial dysfunction and promotes cartilage degeneration through binding molecular chaperone ClpB.Journal of advanced research · 2025Article
- Quality control at the powerhouse: mitochondrial proteostasis dysfunction and disease.Biochemical Society transactions · 2025Article
- HAX1 inhibits apoptosis and promotes maturation of neutrophils.Cell communication and signaling : CCS · 2025Article
- MICU proteins facilitate CaResearch square · 2025Article
- Computational Insights into the Polypharmacological Landscape of BCR-ABL Inhibitors: Emphasis on Imatinib and Nilotinib.Pharmaceuticals (Basel, Switzerland) · 2025Article
- CLPB Deficiency, a Mitochondrial Chaperonopathy With Neutropenia and Neurological Presentation.Journal of inherited metabolic disease · 2025Review
- Dependence of mitochondrial calcium signalling and dynamics on the disaggregase, CLPB.Nature communications · 2025Article
- Hsp90, DnaK, and ClpB collaborate in protein reactivation.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Biophysical and NMR analysis reveals binding affinity between HAX1 and CLPB proteins.Magnetic resonance letters · 2025Article
- Mitochondrial CLPB is a pro-survival factor at the onset of granulocytic differentiation of mouse myeloblastic cells.Apoptosis : an international journal on programmed cell death · 2025Article
- Design principles to tailor Hsp104 therapeutics.Cell reports · 2024Article
- Design principles to tailor Hsp104 therapeutics.bioRxiv : the preprint server for biology · 2024Article
- CLPB disaggregase dysfunction impacts the functional integrity of the proteolytic SPY complex.The Journal of cell biology · 2024Article
- Tuning Hsp104 specificity to selectively detoxify α-synuclein.Molecular cell · 2023Article
- An ankyrin repeat chaperone targets toxic oligomers during amyloidogenesis.Protein science : a publication of the Protein Society · 2023Article
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Cells have evolved specialized protein disaggregases to reverse toxic protein aggregation and restore protein functionality. In nonmetazoan eukaryotes, the AAA+ disaggregase Hsp78 resolubilizes and reactivates proteins in mitochondria. Curiously, metazoa lack Hsp78. Hence, whether metazoan mitochondria reactivate aggregated proteins is unknown. Here, we establish that a mitochondrial AAA+ protein, Skd3 (human ClpB), couples ATP hydrolysis to protein disaggregation and reactivation. The Skd3 ankyrin-repeat domain combines with conserved AAA+ elements to enable stand-alone disaggregase activity. A mitochondrial inner-membrane protease, PARL, removes an autoinhibitory peptide from Skd3 to greatly enhance disaggregase activity. Indeed, PARL-activated Skd3 solubilizes α-synuclein fibrils connected to Parkinson's disease. Human cells lacking Skd3 exhibit reduced solubility of various mitochondrial proteins, including anti-apoptotic Hax1. Importantly, Skd3 variants linked to 3-methylglutaconic aciduria, a severe mitochondrial disorder, display diminished disaggregase activity (but not always reduced ATPase activity), which predicts disease severity. Thus, Skd3 is a potent protein disaggregase critical for human health.
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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.