The Human Autophagy Core Complexes - PubMed
5 hours ago
- #molecular machinery
- #cell biology
- #autophagy
- The human autophagy core machinery includes several key complexes: ULK1 complex (ULK1C), class III phosphatidylinositol 3-kinase complex I (PI3KC3-C1), ATG8 proteins and ATG8ylation machinery, WIPI proteins, ATG2, and ATG9.
- Autophagy initiation can be triggered by clustering of the FIP200 subunit of ULK1C, PI3KC3-C1, or WIPI2, with interactions intensified by feed-forward signaling loops.
- Autophagosome formation starts with ATG9 vesicles, which gather initiation machinery and dock onto a PI3P-positive domain of the endoplasmic reticulum called the omegasome.
- The omegasome contact site is crucial for autophagosome growth, supported by lipid transport through the ATG2 bridge-like lipid transporter.
- The dynamic function of core complexes makes autophagy susceptible to stalling if dynamism fails, with disassembly and dissociation promoted by ULK1 being as important as assembly.