The DOI matches its Crossref record; 46 of the 46 references it cites were found in a registry or an index.
Cargo recognition failure is responsible for inefficient autophagy in Huntington’s disease
Open accessAbstract
Continuous turnover of intracellular components by autophagy is necessary to preserve cellular homeostasis in all tissues. Alterations in macroautophagy, the main process responsible for bulk autophagic degradation, have been proposed to contribute to pathogenesis in Huntington's disease (HD), a genetic neurodegenerative disorder caused by an expanded polyglutamine tract in the huntingtin protein. However, the precise mechanism behind macroautophagy malfunction in HD is poorly understood. In this work, using cellular and mouse models of HD and cells from humans with HD, we have identified a primary defect in the ability of autophagic vacuoles to recognize cytosolic cargo in HD cells. Autophagic vacuoles form at normal or even enhanced rates in HD cells and are adequately eliminated by lysosomes, but they fail to efficiently trap cytosolic cargo in their lumen. We propose that inefficient engulfment of cytosolic components by autophagosomes is responsible for their slower turnover, functional decay and accumulation inside HD cells.
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“Beyond aggregation, polyQ-HTT impairs protein clearance pathways, exacerbating cellular dysfunction, and disrupts autophagy by impairing lysosomal degradation and cargo recognition [190].”
From The Impact of Neurotoxin Proteins Trafficked by Primary Cilia and Extracellular Vesicles in Neurodegenerative Diseases (2025) · cites this paper as [190]
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“Multiple neurodegenerative diseases have dysfunctional mitophagic processes in neurons, as described in Parkinson’s disease (PD) (16), Huntington’s disease (17), amyotrophic lateral sclerosis (ALS) (18), and Alzheimer’s disease (AD) (19,20).”
From Alzheimer's Disease–Associated Amyloid-β Precursor Protein Prevents Aging Stress–Induced Mitophagy and Fumarate Depletion to Improve Antitumor Immunity (2025) · cites this paper as [17]
In the citing paper
“4) an accumulation of autophagy substrates, including p62 (Komatsu et al., 2007a), lipid droplets and damaged mitochondria (Martinez-Vicente et al., 2010), in Tsc2+/- primary neuronal cultures (Figs S5 B, C, D, E);”
From Loss of mTOR-Dependent Macroautophagy Causes Autistic-like Synaptic Pruning Deficits (2014) · cites this paper as Martinez-Vicente et al., 2010
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Cites
LC3, a mammalian homologue of yeast Apg8p, is localized in autophagosome membranes after processing.
Kabeya, Y., Mizushima, N., Ueno, T., Yamamoto, A., Kirisako, T., Noda, T., Kominami, E., Ohsumi, Y., & Yoshimori, T. (2000) · The EMBO Journal · doi:10.1093/emboj/19.21.5720 · Cited by 6,605
Autophagy fights disease through cellular self-digestion
Mizushima, N., Levine, B., Cuervo, A. M., & Klionsky, D. J. (2008) · Nature · doi:10.1038/nature06639 · Cited by 6,452
Self-citationAutophagy regulates lipid metabolism
Singh, R., Kaushik, S., Wang, Y., Xiang, Y., Novak, I., Komatsu, M., Tanaka, K., Cuervo, A. M., & Czaja, M. J. (2009) · Nature · doi:10.1038/nature07976 · Cited by 3,975
Self-citationFission and selective fusion govern mitochondrial segregation and elimination by autophagy
Twig, G., Elorza, A., Molina, A. J. A., Mohamed, H., Wikstrom, J. D., Walzer, G., Stiles, L., Haigh, S. E., Katz, S., Las, G., et al. (2008) · The EMBO Journal · doi:10.1038/sj.emboj.7601963 · Cited by 3,082
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Guidelines for the use and interpretation of assays for monitoring autophagy in higher eukaryotes
Klionsky, D. J., Abeliovich, H., Agostinis, P., Agrawal, D. K., Aliev, G., Askew, D. S., Baba, M., Baehrecke, E. H., Bahr, B. A., Ballabio, A., et al. (2008) · Autophagy · doi:10.4161/auto.5338 · Cited by 2,230
Self-citationDavies, S. W., Turmaine, M., Cozens, B. A., DiFiglia, M., Sharp, A. H., Ross, C. A., Scherzinger, E., Wanker, E. E., Mangiarini, L., & Bates, G. P. (1997) · Cell · doi:10.1016/s0092-8674(00)80513-9 · Cited by 2,188
Impaired Degradation of Mutant α-Synuclein by Chaperone-Mediated Autophagy
Cuervo, A. M., Stefanis, L., Fredenburg, R., Lansbury, P. T., & Sulzer, D. (2004) · Science · doi:10.1126/science.1101738 · Cited by 2,024 · cited 1×
“or in models expressing pathogenic forms of α-synuclei”
BackgroundSelf-citationSarkar, S., Davies, J. E., Huang, Z., Tunnacliffe, A., & Rubinsztein, D. C. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m609532200 · Cited by 1,142
Aggregate-prone proteins with polyglutamine and polyalanine expansions are degraded by autophagy
Ravikumar, B. (2002) · Human Molecular Genetics · doi:10.1093/hmg/11.9.1107 · Cited by 1,099
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Autophagy in Human Health and Disease
Choi, A. M. K., Ryter, S. W., & Levine, B. (2013) · New England Journal of Medicine · doi:10.1056/nejmra1205406 · Cited by 2,583
Phosphorylation of ULK1 (hATG1) by AMP-Activated Protein Kinase Connects Energy Sensing to Mitophagy
Egan, D. F., Shackelford, D. B., Mihaylova, M. M., Gelino, S., Kohnz, R. A., Mair, W., Vasquez, D. S., Joshi, A., Gwinn, D. M., Taylor, R., et al. (2011) · Science · doi:10.1126/science.1196371 · Cited by 2,600
The role of autophagy in neurodegenerative disease
Nixon, R. A. (2013) · Nature Medicine · doi:10.1038/nm.3232 · Cited by 2,059
Huntington's disease: from molecular pathogenesis to clinical treatment
Ross, C. A., & Tabrizi, S. J. (2010) · The Lancet Neurology · doi:10.1016/s1474-4422(10)70245-3 · Cited by 1,816
Signals from the lysosome: a control centre for cellular clearance and energy metabolism
Settembre, C., Fraldi, A., Medina, D. L., & Ballabio, A. (2013) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3565 · Cited by 1,755
Metadata
- Authors
- Martinez-Vicente, M., Talloczy, Z., Wong, E., Tang, G., Koga, H., Kaushik, S., de Vries, R., Arias, E., Harris, S., Sulzer, D., & Cuervo, A. M.
- Affiliations
- Albert Einstein College of Medicine (US)
- Columbia University Irving Medical Center (US)
- Corresponding author
- Sulzer, David
- Venue
- Nature Neuroscience
- Published
- 2010-04-11
- Volume
- 13
- Issue
- 5
- Pages
- 567-576
- ISSN
- 1097-6256 (ISSN-L)
- 1546-1726
- PMC
- PMC2860687
- OpenAlex
- W2129447571
- Cited by
- 885
- References
- 45
- Citations by year
- 2026: 37 · 2025: 53 · 2024: 40 · 2023: 53 · 2022: 49 · 2021: 70 · 2020: 68 · 2019: 58 · 2018: 69 · 2017: 53 · 2016: 47 · 2015: 58 · 2014: 59 · 2013: 47 · 2012: 56
- FWCI
- 22.13
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Aging (R01AG021904, R37AG021904, P01AG031782, AG-021904, AG031782, T32AG023475)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK041918, P01DK041918)
- National Institute of Neurological Disorders and Stroke (P50NS038370)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Genetic Neurodegenerative Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Autophagy in Disease and Therapy
- Health Sciences › Medicine › Genetics (clinical) › Lysosomal Storage Disorders Research
- Keywords
- Huntington's disease, autophagy, cargo recognition, autophagosome formation, autophagosome degradation, lysosomal clearance, neurodegeneration, striatal neurons
- MeSH terms
- Animals, Autophagy, Cells, Cultured, Disease Models, Animal, Enzyme Inhibitors, Humans, Huntington Disease, Immunosuppressive Agents, Lysosomes, Mice, Transgenic, Microtubule-Associated Proteins, Mitochondria, Nerve Tissue Proteins, Neurons, Peptides, Subcellular Fractions, Time Factors, Vinca Alkaloids, Apoptosis, Thapsigargin, Sirolimus, Hepatocytes, Serum, Microscopy, Electron, Transmission, Serotonin Plasma Membrane Transport Proteins, Mice
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