Macroautophagy (autophagy) utilizes a serial of receptors to specifically recognize and degrade autophagy cargoes, including damaged organelles, to maintain cellular homeostasis. Upstream signals spatiotemporally regulate the biological functions of selective autophagy receptors through protein post-translational modifications (PTM) such as phosphorylation. However, it is unclear how acetylation directly controls autophagy receptors in selective autophagy. Here, we report that an ER-phagy receptor FAM134B is acetylated by CBP acetyltransferase, eliciting intense ER-phagy. Furthermore, FAM134B acetylation promoted CAMKII-mediated phosphorylation to sustain a mode of milder ER-phagy. Conversely, SIRT7 deacetylated FAM134B to temper its activities in ER-phagy to avoid excessive ER degradation. Together, this work provides further mechanistic insights into how ER-phagy receptor perceives environmental signals for fine-tuning of ER homeostasis and demonstrates how nucleus-derived factors are programmed to control ER stress by modulating ER-phagy.

中文翻译：

---

由 CBP 和 SIRT7 组成的调节回路调节 FAM134B 介导的 ER 吞噬

巨自噬（autophagy）利用一系列受体特异性识别和降解自噬货物，包括受损的细胞器，以维持细胞稳态。上游信号通过磷酸化等蛋白质翻译后修饰 (PTM) 来时空调节选择性自噬受体的生物学功能。然而，目前尚不清楚乙酰化如何直接控制选择性自噬中的自噬受体。在这里，我们报道了 ER 吞噬受体 FAM134B 被 CBP 乙酰转移酶乙酰化，引发强烈的 ER 吞噬。此外，FAM134B 乙酰化促进 CAMKII 介导的磷酸化以维持较温和的 ER 吞噬模式。相反，SIRT7 使 FAM134B 去乙酰化，以调节其在内质网吞噬中的活性，以避免内质网过度降解。总之，这项工作为 ER 吞噬受体如何感知环境信号以微调 ER 稳态提供了进一步的机制见解，并展示了核源性因子如何通过调节 ER 吞噬来控制 ER 应激。