Daraghmi Mahmoud M, Miller Jacob M, Bailey Connor G, Doss Ellen M, Kalinski Ashley L, Smaldino Philip J, Rubenstein Eric M
Department of Biology, Ball State University.
MicroPubl Biol. 2023 Jan 31;2023. doi: 10.17912/micropub.biology.000738. eCollection 2023.
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 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.
内质网（ER）部分的受体介导自噬周转由巨自噬性内质网自噬介导。我们假设巨自噬性内质网自噬可促进蛋白质毒性应激抗性。我们预测缺乏巨自噬性内质网自噬受体会对潮霉素B表现出增强的敏感性，潮霉素B会降低翻译保真度，并预期会全面破坏蛋白质稳态，包括在内质网处。我们观察到，两种酵母巨自噬性内质网自噬受体（Atg39p或Atg40p）中的任何一种缺失，都会使细胞对潮霉素B的抗性受损，其程度与内质网相关降解（ERAD）泛素连接酶Hrd1p和Doa10p缺失的情况相似。我们的数据与一种模型一致，即巨自噬性内质网自噬和ERAD协同介导内质网蛋白质质量控制。巨自噬性内质网自噬的破坏与神经病变、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病症。
