Autophagy eliminates cytoplasmic material by engulfment in membranous vesicles targeted for lysosome degradation. Nonselective autophagy coordinates sequestration of bulk cargo with the growth of the isolation membrane (IM) in a yet-unknown manner. Here, we show that in the budding yeast Saccharomyces cerevisiae, IMs expand while maintaining a rim sufficiently wide for sequestration of large cargo but tight enough to mature in due time. An obligate complex of Atg24/Snx4 with Atg20 or Snx41 assembles locally at the rim in a spatially extended manner that specifically depends on autophagic PI(3)P. This assembly stabilizes the open rim to promote autophagic sequestration of large cargo in correlation with vesicle expansion. Moreover, constriction of the rim by the PI(3)P-dependent Atg2-Atg18 complex and clearance of PI(3)P by Ymr1 antagonize rim opening to promote autophagic maturation and consumption of small cargo. Tight regulation of membrane rim aperture by PI(3)P thus couples the mechanism and physiology of nonselective autophagy.

自噬通过吞噬溶酶体降解的膜囊泡来消除细胞质物质。非选择性自噬以一种未知的方式协调散装货物的封存与隔离膜（IM）的生长。在这里，我们表明，在出芽的酿酒酵母中，IM 扩张，同时保持足够宽的边缘以隔离大量货物，但又足够紧以在适当的时候成熟。 Atg24/Snx4 与 Atg20 或 Snx41 的专性复合物以空间延伸的方式在边缘局部组装，该方式特别依赖于自噬 PI(3)P。该组件稳定了开放边缘，以促进与囊泡扩张相关的大货物的自噬隔离。此外，PI(3)P 依赖性 Atg2-Atg18 复合物对边缘的收缩以及 Ymr1 对 PI(3)P 的清除会拮抗边缘开放，从而促进自噬成熟和小物质的消耗。因此，PI(3)P 对膜边缘孔径的严格调节将非选择性自噬的机制和生理学结合起来。