A current perspective of autophagosome biogenesis

Abstract

Autophagy is a bulk degradation system induced by cellular stresses such as nutrient starvation. Its function relies on the formation of double-membrane vesicles called autophagosomes. Unlike other organelles that appear to stably exist in the cell, autophagosomes are formed on demand, and once their formation is initiated, it proceeds surprisingly rapidly. How and where this dynamic autophagosome formation takes place has been a long-standing question, but the discovery of Atg proteins in the 1990's significantly accelerated our understanding of autophagosome biogenesis. In this review, we will briefly introduce each Atg functional unit in relation to autophagosome biogenesis, and then discuss the origin of the autophagosomal membrane with an introduction to selected recent studies addressing this problem.

Figure 1

Schematic of autophagosome formation.

Figure 2

Proposed membrane sources of autophagosomal membrane. Upon starvation, Syntaxin-17 (Stx17) facilitates Atg14L accumulation at ER-mitochondria contact sites, inducing the formation of the DFCP1-positive ER cradle/omegasome on the ER. In this model, other membrane sources support the elongation of the forming isolation membrane at the ER cradle/omegasome.