ArticlePLoS computational biology2017
Scaffolding the cup-shaped double membrane in autophagy.
Article in PLoS computational biology, 2017. 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, 46 citations in OpenAlex.
- Condensate-mediated shape transformations of cellular membranes by capillary forces.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Intracerebroventricular BDNF infusion may reduce cerebral ischemia/reperfusion injury by promoting autophagy and suppressing apoptosis.Journal of cellular and molecular medicine · 2024Article
- Mesoscale simulation of biomembranes with FreeDTS.Nature communications · 2024Article
- Determination of the Cryo-EM Structure of ATG9 from Arabidopsis thaliana.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Growing thin - How bulk lipid transport drives expansion of the autophagosome membrane but not of its lumen.Current opinion in cell biology · 2023Review
- Membrane curvature sensing and stabilization by the autophagic LC3 lipidation machinery.Science advances · 2022Article
- A Review of Mechanics-Based Mesoscopic Membrane Remodeling Methods: Capturing Both the Physics and the Chemical Diversity.The Journal of membrane biology · 2022Review
- In situ structural analysis reveals membrane shape transitions during autophagosome formation.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Quantitative Models of Lipid Transfer and Membrane Contact Formation.Contact (Thousand Oaks (Ventura County, Calif.)) · 2022Article
- Multilayered regulation of autophagy by the Atg1 kinase orchestrates spatial and temporal control of autophagosome formation.Molecular cell · 2021Article
- Small but mighty: Atg8s and Rabs in membrane dynamics during autophagy.Biochimica et biophysica acta. Molecular cell research · 2021Review
- Autophagosome biogenesis comes out of the black box.Nature cell biology · 2021Review
- Membrane signalosome: where biophysics meets systems biology.Current opinion in systems biology · 2021Article
- Mechanobiology of Autophagy: The Unexplored Side of Cancer.Frontiers in oncology · 2021Review
- ULK complex organization in autophagy by a C-shaped FIP200 N-terminal domain dimer.The Journal of cell biology · 2020Article
- Subnanometer resolution cryo-EM structure ofAutophagy · 2020Article
- Autophagy in Myelinating Glia.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2020Review
- Mechanistic Insights into the Role of Atg11 in Selective Autophagy.Journal of molecular biology · 2020Review
- Emerging roles of ATG proteins and membrane lipids in autophagosome formation.Cell discovery · 2020Review
- The HIF-1α/LC3-II Axis Impacts Fungal Immunity in Human Macrophages.Infection and immunity · 2019Article
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
Autophagy is a physiological process for the recycling and degradation of cellular materials. Forming the autophagosome from the phagophore, a cup-shaped double-membrane vesicle, is a critical step in autophagy. The origin of the cup shape of the phagophore is poorly understood. In yeast, fusion of a small number of Atg9-containing vesicles is considered a key step in autophagosome biogenesis, aided by Atg1 complexes (ULK1 in mammals) localized at the preautophagosomal structure (PAS). In particular, the S-shaped Atg17-Atg31-Atg29 subcomplex of Atg1 is critical for phagophore nucleation at the PAS. To study this process, we simulated membrane remodeling processes in the presence and absence of membrane associated Atg17. We show that at least three vesicles need to fuse to induce the phagophore shape, consistent with experimental observations. However, fusion alone is not sufficient. Interactions with 34-nm long, S-shaped Atg17 complexes are required to overcome a substantial kinetic barrier in the transition to the cup-shaped phagophore. Our finding rationalizes the recruitment of Atg17 complexes to the yeast PAS, and their unusual shape. In control simulations without Atg17, with weakly binding Atg17, or with straight instead of S-shaped Atg17, the membrane shape transition did not occur. We confirm the critical role of Atg17-membrane interactions experimentally by showing that mutations of putative membrane interaction sites result in reduction or loss of autophagic activity in yeast. Fusion of a small number of vesicles followed by Atg17-guided membrane shape-remodeling thus emerges as a viable route to phagophore formation.
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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 OpenQuestion graph.