The molecular mechanisms regulating the assembly of the autophagy initiation complex

The autophagy initiation complex is brought about via a highly ordered and stepwise assembly process. Two crucial signaling molecules, mTORC1 and AMPK, orchestrate this assembly by phosphorylating/dephosphorylating autophagy-related proteins. Activation of Atg1 followed by recruitment of both Atg9 vesicles and the PI3K complex I to the PAS (phagophore assembly site) are particularly crucial steps in its formation. Ypt1, a small Rab GTPase in yeast cells, also plays an essential role in the formation of the autophagy initiation complex through multiple regulatory pathways. In this review, our primary focus is to discuss how signaling molecules initiate the assembly of the autophagy initiation complex, and highlight the significant roles of Ypt1 in this process. We end by addressing issues that need future clarification. The autophagy initiation complex formation is crucial and involves stepwise assembly. TOR/mTOR and Snf1/AMPK regulate this process by phosphorylating autophagy-related proteins. Atg1/ULK1 and Ypt1/Rab1 are also vital. Additional molecules like histone acetyltransferase (HAT) and lactic acid are involved. We discuss the molecular regulation mechanisms and suggest directions for future investigation. image