Selective clearance of aberrant membrane proteins by TORC1-mediated micro-ER-phagy.

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Tác giả: Yaneris M Alvarado Cartagena, Valeriya Gyurkovska, Rakhilya Murtazina, Nava Segev, Candela Ximenez de Olaso, Sarah F Zhao

Ngôn ngữ: eng

Ký hiệu phân loại: 636.08522 Animal husbandry

Thông tin xuất bản: United States : Cell reports , 2025

Mô tả vật lý:

Bộ sưu tập: NCBI

ID: 690871

Aberrant accumulation and clearance of membrane proteins is associated with disease. Membrane proteins are inserted first to the endoplasmic reticulum (ER). During normal growth, two quality control (QC) processes, ER-associated degradation and macro-ER-phagy, deliver misfolded and excess membrane proteins for degradation in the proteasome and lysosome, respectively. We show that in yeast during normal growth, ER-QC is constitutive, since none of the stress-induced signaling pathways-nutritional, proteotoxic, or heat-are involved. In mutant cells defective in ER-QC, misfolded or excess proteins accumulate and nutritional stress, but not proteotoxic or heat stress, can stimulate their clearance. Early during nutritional stress, clearance occurs in the lysosome through a selective micro-ER-phagy pathway dependent on the ubiquitin ligase Rsp5, its Ssh4 adaptor, and ESCRT. In contrast, only a fraction of normal membrane proteins is degraded much later via macro-autophagy. Because the pathways explored here are conserved, nutritional stress emerges as a possible way for clearing disease-associated membrane proteins.
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