ER-phagy, the selective autophagy of endoplasmic reticulum (ER), safeguards organelle homeostasis by eliminating misfolded proteins and regulating ER size. ER-phagy can occur by macroautophagic and microautophagic mechanisms. While dedicated machinery for macro-ER-phagy has been discovered, the molecules and mechanisms mediating micro-ER-phagy remain unknown. Here, we first show that micro-ER-phagy in yeast involves the conversion of stacked cisternal ER into multilamellar ER whorls during microautophagic uptake into lysosomes. Second, we identify the conserved Nem1-Spo7 phosphatase complex and the ESCRT machinery as key components for micro-ER-phagy. Third, we demonstrate that macro- and micro-ER-phagy are parallel pathways with distinct molecular requirements. Finally, we provide evidence that the ESCRT machinery directly functions in scission of the lysosomal membrane to complete the microautophagic uptake of ER. These findings establish a framework for a mechanistic understanding of micro-ER-phagy and, thus, a comprehensive appreciation of the role of autophagy in ER homeostasis.

中文翻译：

---

ESCRT 机制介导酵母内质网的选择性微自噬。


ER 自噬是内质网 (ER) 的选择性自噬，通过消除错误折叠的蛋白质和调节 ER 大小来维护细胞器稳态。内质网吞噬可以通过巨自噬和微自噬机制发生。虽然已经发现了大内质网自噬的专用机制，但介导微内质网自噬的分子和机制仍然未知。在这里，我们首先表明酵母中的微内质网吞噬涉及在微自噬摄取到溶酶体期间将堆积的内质网转化为多层内质网螺旋。其次，我们将保守的 Nem1-Spo7 磷酸酶复合物和 ESCRT 机制确定为微 ER 吞噬的关键组件。第三，我们证明宏内质网自噬和微内质网自噬是具有不同分子要求的平行途径。最后，我们提供证据表明 ESCRT 机制直接在溶酶体膜的裂解中发挥作用，以完成 ER 的微自噬摄取。这些发现为理解微内质网自噬的机制建立了一个框架，从而全面了解自噬在内质网稳态中的作用。