ArticleeLife2025
The triad interaction of ULK1, ATG13, and FIP200 is required for ULK complex formation and autophagy.
Article in eLife, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed.
- Autophagy and selective autophagy receptors: Key players against Alzheimer's disease.Neural regeneration research · 2026Article
- Article
- MicroRNA-Mediated Regulation of Brain Aging Hallmarks: Implications for Neurodegeneration and Neural Recovery.Brain and behavior · 2026Review
- Targeting ULK1 and USP20 to modulate autophagy and chemosensitivity in cancer cell lines.Biomedical reports · 2026Article
- ULK1 activates NCOA4‑mediated ferritinophagy via the Beclin1/VPS34 complex in cardiomyocyte hypertrophy.Molecular medicine reports · 2026Article
- Membrane atg8ylation and autophagy in protection against Mycobacterium tuberculosis.Journal of immunology (Baltimore, Md. : 1950) · 2026Review
- Ferritinophagy: molecular mechanisms and its crosstalk with ferroptosis in chronic respiratory diseases.Cell biology and toxicology · 2026Review
- Ambiguous Role of p53 in Transcription-Dependent Tumor Cell Death.International journal of molecular sciences · 2026Review
- Therapeutic Promise of Mitophagy in Cancer: Advancing from Small-Molecule Regulation to Nanotechnology-Enhanced Targeting Therapy.Theranostics · 2026Review
- The clinical significance and prognostic implication of autophagy-related gene 13 in human gastric cancer.Frontiers in oncology · 2026Article
- The role of microRNAs on autophagy in cervical cancer: review.Discover oncology · 2025Review
- Autophagy, ER-phagy and ER Dynamics During Cell Differentiation.Journal of molecular biology · 2025Review
- ER-driven Contact Sites in Autophagosome Biogenesis Sequence.Contact (Thousand Oaks (Ventura County, Calif.))Review
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Authors and funding
5 authors.
Funding
Abstract
In mammals, autophagosome formation, a central event in autophagy, is initiated by the ULK complex comprising ULK1/2, FIP200, ATG13, and ATG101. However, the structural basis and mechanism underlying the ULK complex assembly have yet to be fully clarified. Here, we predicted the core interactions organizing the ULK complex using AlphaFold, which proposed that the intrinsically disordered region of ATG13 engages the bases of the two UBL domains in the FIP200 dimer via two phenylalanines and also binds the tandem microtubule-interacting and transport domain of ULK1, thereby yielding the 1:1:2 stoichiometry of the ULK1-ATG13-FIP200 complex. We validated the predicted interactions by point mutations and demonstrated direct triad interactions among ULK1, ATG13, and FIP200 in vitro and in cells, wherein each interaction was additively important for autophagic flux. These results indicate that the ULK1-ATG13-FIP200 triadic interaction is crucial for autophagosome formation and provides a structural basis and insights into the regulation mechanism of autophagy initiation in mammals.
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