School of Life Science and Technology, Tokyo Institute of Technology, Yokohama, Japan.
Autophagy. 2022 Dec;18(12):3046-3047. doi: 10.1080/15548627.2022.2069957. Epub 2022 Apr 29.
Recent studies have revealed that even the nucleus can be degraded by selective macroautophagy (hereafter macronucleophagy). In , the nuclear envelope (NE) protein Atg39 acts as a macronucleophagy receptor that mediates sequestration of nucleus-derived double-membrane vesicles (NDVs) into phagophores. The outer and inner membranes of these NDVs are derived from the outer and inner nuclear membranes (ONM and INM), respectively, and the lumen contains nucleoplasmic material. Little was known about the mechanisms underlying macronucleophagy, including how the two nuclear membranes are coordinately deformed to generate NDVs and what nuclear components are preferentially loaded into or rather eliminated from NDVs. We found that Atg39 links the ONM and INM through the ONM-embedded transmembrane domain and INM-associated amphipathic helices (APHs). These APHs are important for Atg39 anchoring to the NE and autophagosome formation-coupled Atg39 clustering in the NE. In addition, the overaccumulation of Atg39 in the NE caused NE protrusion toward the cytoplasm depending on the APHs. These results allowed us to propose the mechanism by which Atg39 conducts NDV formation in coordination with autophagosome formation during macronucleophagy.
最近的研究表明，即使是细胞核也可以被选择性的巨自噬（以下简称巨核自噬）降解。在[文章标题]中，核包膜（NE）蛋白 Atg39 作为巨核自噬受体，介导来源于细胞核的双层膜泡（NDVs）被隔离到吞噬体中。这些 NDV 的外膜和内膜分别来源于核外膜（ONM）和核内膜（INM），腔内容纳核质物质。关于巨核自噬的机制知之甚少，包括两个核膜如何协调变形以产生 NDV，以及哪些核成分优先被装入或从 NDV 中消除。我们发现 Atg39 通过 ONM 嵌入式跨膜结构域和 INM 相关的两亲性螺旋（APHs）将 ONM 和 INM 连接起来。这些 APHs 对于 Atg39 在 NE 中的锚定和与自噬体形成偶联的 Atg39 在 NE 中的聚集是重要的。此外，由于 APHs 的存在，Atg39 在 NE 中的过度积累会导致 NE 向细胞质突出。这些结果使我们能够提出 Atg39 与巨核自噬过程中的自噬体形成协调地进行 NDV 形成的机制。
