ArticleNature medicine2011
Mutant huntingtin binds the mitochondrial fission GTPase dynamin-related protein-1 and increases its enzymatic activity.
Article in Nature medicine, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 320 papers.
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Who cites it
320 citing papers in PubMed, 541 citations in OpenAlex.
- Mitochondrial quality control in health and disease: mechanisms and therapeutic targets.Signal transduction and targeted therapy · 2026Review
- SUMOylation in Mitochondrial Quality Control: Mechanisms and Implications for Neurodegenerative Disease.Molecular neurobiology · 2026Review
- Cortistatin as a modulator of inflammatory and mitochondrial dysfunction in Huntington´s disease.Journal of neuroinflammation · 2026Article
- The Legionella effector RidL binds the large fission GTPase Drp1 to promote mitochondrial fragmentation.EMBO reports · 2026Article
- Huntingtin polyglutamine expansions misdirect axonal transport by perturbing motor and adaptor recruitment.iScience · 2026Article
- Review
- Huntingtin and its allies at the cortico-striatal synapse.Cell death & disease · 2026Review
- Neuronal mitochondrial dynamics: roles in brain disorders and therapeutic potential.Acta pharmacologica Sinica · 2026Article
- Novel small molecule derivatives improve survivability in the cellular model of Huntington's diseaseRSC medicinal chemistry · 2026Article
- Stress-induced mitochondrial fragmentation in endothelial cells disrupts blood-retinal barrier integrity causing neurodegeneration.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Neuronal mitochondrial disaggregase CLPB ameliorates Huntington's disease pathology in mice.Theranostics · 2026Article
- Maternal monosodium glutamate exposure disrupts leptin and insulin signaling in the hypothalamus, activating NF-κB and mTOR inflammatory pathways, contributing to metabolic dysfunction in male offspring.International journal of obesity (2005) · 2026Article
- Mitochondrial dysfunction in cellular senescence: a bridge to neurodegenerative disease.npj aging · 2025Review
- Mitochondrial-Derived Peptides: Implication in the Therapy of Neurodegenerative Diseases.Molecular neurobiology · 2025Review
- Neurobiology of mitochondrial dynamics in sleep.The Journal of physiology · 2025Review
- Brain organoid models of Huntington's disease shift the focus towards neurodevelopment.Disease models & mechanisms · 2025Article
- Review
- Endothelial mitochondria in the blood-brain barrier.Fluids and barriers of the CNS · 2025Review
- Huntingtin preserves mitochondrial genome integrity in neurons, which is impaired in Huntington's disease.bioRxiv : the preprint server for biology · 2025Article
- Mitochondria-Associated Membranes: A Key Point of Neurodegenerative Diseases.CNS neuroscience & therapeutics · 2025Review
260 more citing papers are in PubMed but not listed here.
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Authors and funding
17 authors at 5 institutions in 3 countries.
Funding
Abstract
Huntington's disease is an inherited and incurable neurodegenerative disorder caused by an abnormal polyglutamine (polyQ) expansion in huntingtin (encoded by HTT). PolyQ length determines disease onset and severity, with a longer expansion causing earlier onset. The mechanisms of mutant huntingtin-mediated neurotoxicity remain unclear; however, mitochondrial dysfunction is a key event in Huntington's disease pathogenesis. Here we tested whether mutant huntingtin impairs the mitochondrial fission-fusion balance and thereby causes neuronal injury. We show that mutant huntingtin triggers mitochondrial fragmentation in rat neurons and fibroblasts of individuals with Huntington's disease in vitro and in a mouse model of Huntington's disease in vivo before the presence of neurological deficits and huntingtin aggregates. Mutant huntingtin abnormally interacts with the mitochondrial fission GTPase dynamin-related protein-1 (DRP1) in mice and humans with Huntington's disease, which, in turn, stimulates its enzymatic activity. Mutant huntingtin-mediated mitochondrial fragmentation, defects in anterograde and retrograde mitochondrial transport and neuronal cell death are all rescued by reducing DRP1 GTPase activity with the dominant-negative DRP1 K38A mutant. Thus, DRP1 might represent a new therapeutic target to combat neurodegeneration in Huntington's disease.
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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.