Abstract：
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.
摘要：
自噬通过吞噬靶向溶酶体降解的膜囊泡来消除细胞质物质。非选择性自噬以未知的方式协调散装货物的隔离与隔离膜（IM）的生长。这里,我们表明，在出芽酵母酿酒酵母中，IM扩展，同时保持边缘足够宽，以隔离大型货物，但足够紧密，可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，具体取决于自噬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型货物的自噬隔离。此外，PI（3）P依赖性Atg2-Atg18复合物对轮缘的收缩和Ymr1对PI（3）P的清除拮抗轮缘开放，以促进自噬成熟和小货物的消耗。PI（3）P对膜边缘孔径的紧密调节因此与非选择性自噬的机制和生理学结合。
