ArticleNature structural & molecular biology2024
Reduction of DHHC5-mediated beclin 1 S-palmitoylation underlies autophagy decline in aging.
Article in Nature structural & molecular biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 36 citations in OpenAlex.
- Cellular Senescence and Aging: Mechanisms, Disease Convergence, and Therapeutic Frontiers.MedComm · 2026Review
- Protein Palmitoylation as a Molecular Switch Linking Regulated Cell Death and Disease.Biomolecules · 2026Review
- From lipid modification to cell death: the diverse roles of S-palmitoylation in cell fate decisions.Cell communication and signaling : CCS · 2026Review
- CD36 and Its Role in Obesity.Obesity reviews : an official journal of the International Association for the Study of Obesity · 2026Review
- Lactucopicrin promotes the autophagic degradation of MAP2K4/MKK4 by mediating CCDC50 palmitoylation to alleviate osteoarthritis progression.Autophagy · 2026Article
- S-palmitoylation in ferroptosis: molecular mechanisms, modulators, and interplay with autophagy.Apoptosis : an international journal on programmed cell death · 2026Review
- Bioinformatics Analysis of ZDHHC-protein Acyltransferase for Predicting the Rupture of Aneurysmal Subarachnoid Hemorrhage.Current neurovascular research · 2026Article
- The palmitoylation code in cell death signaling: from molecular mechanisms to therapeutic opportunities.Frontiers in cell and developmental biology · 2026Review
- Protein S-Palmitoylation as Potential Therapeutic Target for Dermatoses.Biomolecules · 2025Review
- A Novel Palmitoylation-Related Molecular Signature for Predicting and Therapeutically Targeting Alzheimer's Disease.Molecular neurobiology · 2025Article
- Multiple Mechanisms and Therapeutic Strategies for the Involvement of AMPK in the Development of Alzheimer's Disease.Molecular neurobiology · 2025Review
- Neonatal sevoflurane exposures inhibits DHHC5-mediated palmitoylation of TfR1 in oligodendrocytes, leading to hypomyelination and neurological impairments.Journal of advanced research · 2025Article
- S-palmitoylation coordinates the trafficking of ATG9A to mediate autophagy initiation.Autophagy · 2025Article
- The connection between autophagy and Alzheimer's disease.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2025Review
- The Role of the Beclin1 Complex in Rab9-Dependent Alternative Autophagy.International journal of molecular sciences · 2025Review
- Palmitic acid and palmitoylation in cancer: Understanding, insights, and challenges.Innovation (Cambridge (Mass.)) · 2025Review
- Role of S-palmitoylation in digestive system diseases.Cell death discovery · 2025Review
- The human autophagy-initiating complexes ULK1C and PI3KC3-C1.The Journal of biological chemistry · 2025Review
- Protein lipidation in the tumor microenvironment: enzymology, signaling pathways, and therapeutics.Molecular cancer · 2025Review
- Mechanisms and functional implications of ZDHHC5 in cellular physiology and disease.Journal of lipid research · 2025Review
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Autophagy is a lysosome-dependent degradation pathway essential for cellular homeostasis, which decreases with age. However, it is unclear how aging induces autophagy decline. Here we show the role of protein S-palmitoylation in autophagy. We identify the palmitoyl acyltransferase DHHC5 as a regulator of autophagy by mediating the palmitoylation of beclin 1, which in turn promotes the formation of ATG14L-containing class III phosphatidylinositol-3-kinase complex I and its lipid kinase activity by promoting the hydrophobic interactions between beclin 1 and adapter proteins ATG14L and VPS15. In aging brains of human and nonhuman primate, the levels of DHHC5 exhibit a marked decrease in expression. We show that DHHC5 deficiency in neurons leads to reduced cellular protein homeostasis in two established murine models of Alzheimer's disease, which exaggerates neurodegeneration in an autophagy-dependent manner. These findings identify reduction of DHHC5-mediated beclin 1 S-palmitoylation as an underlying mechanism by which aging induces autophagy decline.
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Registered trials
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 Socratic graph.