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The human autophagy-initiating complexes ULK1C and PI3KC3-C1

Minghao Chen1, James Hurley2

  • 1Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, California, USA; California Institute for Quantitative Biosciences, University of California, Berkeley, Berkeley, California, USA; Aligning Science Across Parkinson's (ASAP) Collaborative Research Network, Chevy Chase, Maryland, USA.

The Journal of Biological Chemistry
|June 21, 2025
PubMed

The unc-51-like kinase complex (ULK1C) and the class III phosphatidylinositol 3-kinase complex I (PI3KC3-C1) are the key regulators of macroautophagy initiation. Understanding the assembly and coordination of these two complexes is essential for deciphering their cellular regulation and targeting them for therapeutic enhancement. This review highlights recent advances in our understanding of the structural organization and activation mechanisms of ULK1C and PI3KC3-C1 at the molecular level and discusses their roles within the protein interaction network governing autophagy initiation.

Keywords:
ATG101ATG13ATG14BECN1Beclin-1FIP200ULK1VPS15VPS34autophagycryo-EMmitophagyphosphoinositide kinaseprotein kinase

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