Department of Biochemistry, and Department of Cardiology of Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
International Institutes of Medicine, The Fourth Affiliated Hospital of Zhejiang University School of Medicine, Yiwu, Zhejiang, China.
Autophagy. 2024 Jan;20(1):210-211. doi: 10.1080/15548627.2023.2252723. Epub 2023 Aug 31.
Reticulophagy is an evolutionarily conserved mechanism essential to maintain the endoplasmic reticulum (ER) homeostasis. A series of studies identified a panel of reticulophagy receptors. However, it remains unclear how these receptors sense upstream signals for spatiotemporal control of reticulophagy and how ER is fragmented into small pieces for sequestration into phagophores. Recently, we and others showed that the oligomerization of RETREG1/FAM134B (reticulophagy regulator 1), an reticulophagy receptor, triggers the scission of ER membrane to facilitate reticulophagy. Furthermore, we demonstrated that upstream signals are transduced by sequential phosphorylation and acetylation of RETREG1, which stimulate its oligomerization, ER fragmentation and reticulophagy. Our work provides further mechanistic insights into how reticulophagy receptor conveys cellular signals to fine-tune of ER homeostasis.: ER, endoplasmic reticulum; MAP1LC3, microtubule-associated protein light chain 3; RETREG1, reticulophagy regulator 1; RHD, reticulon-homology domain.
自噬是一种进化上保守的机制，对于维持内质网（ER）的稳态至关重要。一系列研究确定了一组自噬受体。然而，这些受体如何感知上游信号以实现自噬的时空控制，以及 ER 如何被分割成小块并被隔离到吞噬体中，目前仍不清楚。最近，我们和其他人的研究表明，自噬受体 RETREG1/FAM134B（自噬调节因子 1）的寡聚化触发 ER 膜的分裂，从而促进自噬。此外，我们还证明，上游信号通过 RETREG1 的顺序磷酸化和乙酰化转导，刺激其寡聚化、ER 片段化和自噬。我们的工作进一步深入了解了自噬受体如何传递细胞信号来精细调节 ER 稳态。：ER，内质网；MAP1LC3，微管相关蛋白轻链 3；RETREG1，自噬调节因子 1；RHD，网蛋白同源结构域。
