Atg9 vesicles are an important membrane source during early steps of autophagosome formation

Abstract

Atg9-containing vesicles assemble to the preautophagosomal structure and eventually are incorporated into the autophagosomal outer membrane.

A current perspective of autophagosome biogenesis

“…Mammalian Atg9 may not be stably incorporated into isolation membranes or autophagosomes even though it may transiently interact with these structures. In contrast, however, yeast Atg9 has been detected on isolation membranes and autophagosomes, suggesting the incorporation of Atg9 vesicles into these membranes [57]. Interestingly, typically only a few Atg9 vesicles are recruited during one round of autophagosome formation in yeast [57].…”

“…In contrast, however, yeast Atg9 has been detected on isolation membranes and autophagosomes, suggesting the incorporation of Atg9 vesicles into these membranes [57]. Interestingly, typically only a few Atg9 vesicles are recruited during one round of autophagosome formation in yeast [57]. Since so few Atg9 vesicles (30-60 nm diameter) cannot provide the lipid amount of one autophagosome (300-900 nm diameter), it is likely that other membrane sources exist.…”

“…The PAS localization of Atg9 requires postGolgi vesicle-trafficking machinery [58][59][60][61][62]. Yeast Atg9 was also found on isolation membranes and autophagosomes [57]. In mammals, Atg9 partially localizes to the trans-Golgi network and endosomes, and starvation npg induces the exit of Atg9 vesicles from the trans-Golgi network and transient colocalization of Atg9 with the autophagosome marker LC3 when visualized by fluorescence microscopy [26].…”

“…Although Atg9 is required for the accumulation of most of the downstream Atg proteins [19,56], its function is still enigmatic. In yeast, Atg9 has been shown to localize on small vesicles of 30-60 nm diameter (Atg9 vesicles) [57], which localize to the PAS and in the cytoplasm. The PAS localization of Atg9 requires postGolgi vesicle-trafficking machinery [58][59][60][61][62].…”

Autophagy at the crossroads of catabolism and anabolism

“…Although evidence supports the idea that nucleation of the isolation membrane occurs at a distinct site emanating from the endoplasmic reticulum (ER), termed the omegasome 17 , other sources of membrane contribute to autophagosome formation, including ER-Golgi intermediate compartments, ERmitochondri a junctions, mitochondria, endosomes and the plasma membrane [17][18][19][20][21][22] . Taken together, these studies highlight the complexities of autophagy initiation in mammals.…”