Macro-ER-phagy receptors Atg39p and Atg40p confer resistance to aminoglycoside hygromycin B in S. cerevisiae.
Macro-ER-phagy receptors Atg39p and Atg40p confer resistance to aminoglycoside hygromycin B in S. cerevisiae.
复制标题
DOI：
10.17912/micropub.biology.000738
复制
发表时间：
2023
影响因子：
--
通讯作者：
Rubenstein, Eric M
中科院分区：
文献类型：
--
作者：
Daraghmi, Mahmoud M;Miller, Jacob M;Bailey, Connor G;Doss, Ellen M;Kalinski, Ashley L;Smaldino, Philip J;Rubenstein, Eric M
受体介导的内质网（ER）部分的自噬周转是由巨ER-吞噬介导的。我们假设巨噬细胞ER-吞噬促进蛋白毒性应激抗性。我们预测缺乏巨噬细胞ER-吞噬受体的酿酒酵母将表现出对潮霉素B的增强的敏感性，潮霉素B降低了翻译保真度，并且预计会全面破坏蛋白质稳态，包括在ER。我们观察到，两种酵母巨噬细胞ER-吞噬受体（Atg 39 p或Atg 40 p）的丢失损害了细胞对潮霉素B的抗性，其程度与ER相关降解（ERAD）泛素连接酶Hrd 1 p和Doa 10 p的丢失相似。我们的数据是一致的模型，其中宏ER-phagy和ERAD合作，介导ER蛋白质的质量控制。巨噬细胞ER吞噬功能的破坏与神经病、痴呆和癌症有关。介导蛋白质质量控制的能力减弱可能导致这些情况。
Receptor-mediated autophagic turnover of portions of the endoplasmic reticulum (ER) is mediated by macro-ER-phagy. We hypothesized macro-ER-phagy promotes proteotoxic stress resistance. We predicted Saccharomyces cerevisiae lacking macro-ER-phagy receptors would exhibit enhanced sensitivity to hygromycin B, which reduces translational fidelity and is expected to globally disrupt protein homeostasis, including at the ER. We observed that loss of either of two yeast macro-ER-phagy receptors (Atg39p or Atg40p) compromised cellular resistance to hygromycin B to a similar extent as loss of ER-associated degradation (ERAD) ubiquitin ligases Hrd1p and Doa10p. Our data are consistent with a model whereby macro-ER-phagy and ERAD collaborate to mediate ER protein quality control. Disruptions of macro-ER-phagy have been linked to neuropathy, dementia, and cancer. A dampened capacity to mediate protein quality control may contribute to these conditions.