The Atg proteins involved in autophagosome formation consist of several functional units: Atg1 kinase and its regulators, the PI3K complex, Atg9, the Atg2-Atg18 complex, and two ubiquitin-like conjugation systems.Mammals contain counterparts for most yeast Atg proteins as well as some additional factors that are specific to higher eukaryotes. During canonical autophagy, Atg1 associates with Atg13, Atg17, Atg29 and Atg31. In contrast, during the Cvt pathway, Atg1 interacts with Atg11, Atg13, Atg20, Atg24 and Vac8.  the mTORC1-dependent regulation of the ULK1–ATG13–FIP200–ATG101 complex has been deciphered. Under nutrient-rich conditions, mTORC1 associates with the ULK1–ATG13–FIP200–ATG101 complex and phosphorylates ULK1 and ATG13. Under starvation conditions or upon treatment with mTOR inhibitors, mTORC1 dissociates from this mega-complex, and the inhibitory mTOR-dependent phospho-sites within ULK1 and ATG13 become dephosphorylated. Active ULK1 then autophosphorylates and phosphorylates ATG13 and FIP200, ultimately leading to the initiation of autophagosome formation.The phospho-status of the ULK1–ATG13–FIP200–ATG101 complex is central for the regulation of autophagic processes. In general, global phosphorylation of ULK1 and ATG13 is decreased under starvation conditions and FIP200 phosphorylation is decreased under fed conditions.

References

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