ArticleProceedings of the National Academy of Sciences of the United States of America2014
Potential function for the Huntingtin protein as a scaffold for selective autophagy.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 179 papers, 1 of them a synthesis that pooled it.
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Who cites it
179 citing papers in PubMed, 1 synthesis or guideline pooled it, 296 citations in OpenAlex.
- Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)Autophagy · 2021Guideline
- Cell Death in Neurodegenerative Diseases: Molecular Mechanisms and Therapeutic Targets.MedComm · 2026Review
- The DNA/RNA autophagy protein SIDT2 as a novel neuropathological hallmark in Huntington disease.Brain pathology (Zurich, Switzerland) · 2026Article
- The role of phospho-ubiquitin in mitochondrial health and diseases.The Journal of biological chemistry · 2026Review
- Huntingtin and its allies at the cortico-striatal synapse.Cell death & disease · 2026Review
- ALS and Huntington Disease: Unraveling the Connections between TDP-43 and Huntingtin.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2026Review
- Huntingtin knockdown dysregulates autophagic degradation of Apolipoprotein E.Journal of Huntington's disease · 2026Article
- SQSTM1/p62 UFMylation Enhances Autophagic Clearance of Pathogenic Mutant Huntingtin.International journal of biological sciences · 2026Article
- Autophagy and mitophagy at the synapse and beyond: implications for learning, memory and neurological disorders.Autophagy · 2026Review
- Navigating the Autophagy Maze: ATG and Their Impact on Neurodegenerative Diseases.Molecular neurobiology · 2025Review
- Dynamics of autophagy in response to high linear energy transfer radiation and cancer.Korean journal of clinical oncology · 2025Review
- Post-Translational Modifications of Huntingtin: Mechanistic Insights and Therapeutic Opportunities in Huntington's Disease.International journal of molecular sciences · 2025Review
- Pathobiology of the autophagy-lysosomal pathway in the Huntington's disease brain.Acta neuropathologica communications · 2025Article
- Review
- Huntingtin preserves mitochondrial genome integrity in neurons, which is impaired in Huntington's disease.bioRxiv : the preprint server for biology · 2025Article
- Intersecting impact of CAG repeat and huntingtin knockout in stem cell-derived cortical neurons.Neurobiology of disease · 2025Article
- Article
- Reduced Palmitoylation of SQSTM1/p62 in Huntington Disease Is Associated With Impaired Autophagy.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Article
- Modulation of autophagy by melatonin and its receptors: implications in brain disorders.Acta pharmacologica Sinica · 2025Review
119 more citing papers are in PubMed but not listed here.
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Authors and funding
18 authors at 8 institutions in 4 countries.
Funding
Abstract
Although dominant gain-of-function triplet repeat expansions in the Huntingtin (HTT) gene are the underlying cause of Huntington disease (HD), understanding the normal functions of nonmutant HTT protein has remained a challenge. We report here findings that suggest that HTT plays a significant role in selective autophagy. Loss of HTT function in Drosophila disrupts starvation-induced autophagy in larvae and conditional knockout of HTT in the mouse CNS causes characteristic cellular hallmarks of disrupted autophagy, including an accumulation of striatal p62/SQSTM1 over time. We observe that specific domains of HTT have structural similarities to yeast Atg proteins that function in selective autophagy, and in particular that the C-terminal domain of HTT shares structural similarity to yeast Atg11, an autophagic scaffold protein. To explore possible functional similarity between HTT and Atg11, we investigated whether the C-terminal domain of HTT interacts with mammalian counterparts of yeast Atg11-interacting proteins. Strikingly, this domain of HTT coimmunoprecipitates with several key Atg11 interactors, including the Atg1/Unc-51-like autophagy activating kinase 1 kinase complex, autophagic receptor proteins, and mammalian Atg8 homologs. Mutation of a phylogenetically conserved WXXL domain in a C-terminal HTT fragment reduces coprecipitation with mammalian Atg8 homolog GABARAPL1, suggesting a direct interaction. Collectively, these data support a possible central role for HTT as an Atg11-like scaffold protein. These findings have relevance to both mechanisms of disease pathogenesis and to therapeutic intervention strategies that reduce levels of both mutant and normal HTT.
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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.