Category Ranking
98%
Total Visits
921
Avg Visit Duration
2 minutes
Citations
20
Article Abstract
Autophagy is crucial for degrading and recycling cellular components. Fusion between autophagosomes and lysosomes is pivotal, directing autophagic cargo to degradation. This process is driven by STX17-SNAP29-VAMP8 and STX7-SNAP29-YKT6 in mammalian cells. However, the interaction between STX17 and YKT6 and its significance remain to be revealed. In this study, we challenge the notion that STX17 and YKT6 function independently in autophagosome-lysosome fusion. YKT6, through its SNARE domain, forms a complex with STX17 and SNAP29 on autophagosomes, enhancing autophagy flux. VAMP8 displaces YKT6 from this complex, leading to the formation of the fusogenic complex STX17-SNAP29-VAMP8. We demonstrated that the YKT6-SNAP29-STX17 complex facilitates both lipid and content mixing driven by STX17-SNAP29-VAMP8, suggesting a priming role of YKT6 for efficient membrane fusion. Our results provide a potential regulation mechanism of autophagosome-lysosome fusion, highlighting the importance of YKT6 and its interactions with STX17 and SNAP29 in promoting autophagy flux.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.celrep.2024.113760 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
VAMP8 stabilization by DRAM1 enables autophagosome-lysosome fusion and promotes metastatic extravasation.
Autophagy
September 2025
National "111" Center for Cellular Regulation and Molecular Pharmaceutics, Key Laboratory of Fermentation Engineering (Ministry of Education), Cooperative Innovation Center of Industrial Fermentation (Ministry of Education & Hubei Province), Hubei Key Laboratory of Industrial Microbiology, Hubei Uni
Autophagosome-lysosome fusion, essential for macroautophagy/autophagy completion, requires the STX17-SNAP29-VAMP8 SNARE complex. While VAMP8 is crucial, its regulatory mechanisms remain incompletely understood. Here, we identify DRAM1 (DNA damage regulated autophagy modulator 1) as a key interactor and stabilizer of VAMP8 on lysosomes.
View Article and Find Full Text PDFSystemic Neurodegeneration and Brain Aging: Multi-Omics Disintegration, Proteostatic Collapse, and Network Failure Across the CNS.
Biomedicines
August 2025
Medical Section, Romanian Academy, 010071 Bucharest, Romania.
Neurodegeneration is increasingly recognized not as a linear trajectory of protein accumulation, but as a multidimensional collapse of biological organization-spanning intracellular signaling, transcriptional identity, proteostatic integrity, organelle communication, and network-level computation. This review intends to synthesize emerging frameworks that reposition neurodegenerative diseases (ND) as progressive breakdowns of interpretive cellular logic, rather than mere terminal consequences of protein aggregation or synaptic attrition. The discussion aims to provide a detailed mapping of how critical signaling pathways-including PI3K-AKT-mTOR, MAPK, Wnt/β-catenin, and integrated stress response cascades-undergo spatial and temporal disintegration.
View Article and Find Full Text PDFMiR-7 inhibits progression of glioblastoma by impairing autophagy resolution, energy metabolism and ECM remodeling.
J Exp Clin Cancer Res
August 2025
IMDEA Research Institute of Food & Health Sciences, Madrid, Spain.
Background: Due to the poor prognosis of patients suffering malignant brain tumors such as glioblastoma multiforme (GBM), the search for new therapeutic strategies with more efficacy and higher survival rate is of utmost urgency. Growing evidence suggests that alterations in autophagy and metabolism critically contribute to the pathogenesis and progression of GBM. In this context, microRNAs are known to regulate autophagy and associated cellular functions, which point them as promising therapeutic candidates.
View Article and Find Full Text PDFDRAM1 promotes the stability of lysosomal VAMP8 to enhance autolysosome formation and facilitates the extravasation.
Nat Commun
July 2025
National "111" Center for Cellular Regulation and Molecular Pharmaceutics, Key Laboratory of Fermentation Engineering (Ministry of Education), Cooperative Innovation Center of Industrial Fermentation (Ministry of Education & Hubei Province), Hubei Key Laboratory of Industrial Microbiology, Hubei Uni
Autophagy classically functions to protect cells and organisms during stressful conditions by catabolizing intracellular components to maintain energy homeostasis. Lysosome-autophagosome fusion is a critical step in emptying degraded unwanted contents. However, the mechanism of autophagosome fusion with lysosomes is still not fully understood.
View Article and Find Full Text PDFPhosphoribosyl ubiquitination of SNARE proteins regulates autophagy during Legionella infection.
EMBO J
August 2025
Institute of Biochemistry II, Faculty of Medicine, Goethe University, Frankfurt, Germany.
Legionella pneumophila is an intracellular pathogen that causes Legionnaires' disease. The bacteria release effector proteins, some of which remodel host autophagic-lysosomal pathways. One such effector is RavZ, which delipidates ATG8 proteins, making compromising autophagy in Legionella-infected cells.
View Article and Find Full Text PDF