西班牙巴塞罗那科技学院Elvan Böke团队近期取得重要工作进展，他们研究提出，小鼠卵母细胞在降解性超细胞器中隔离聚集蛋白，维持蛋白质稳态。相关研究成果2024年2月20日在线发表于《细胞》杂志上。

据介绍，卵母细胞是体内寿命最长的细胞之一，需要保存细胞质以支持胚胎的正常发育。蛋白质聚集是对长寿细胞内稳态的主要威胁。卵母细胞在延长寿命期间如何应对蛋白质聚集尚不清楚。

研究人员发现小鼠卵母细胞内溶酶体囊泡组装体（ELVA）的特殊隔间中积累蛋白质聚集体。结合活细胞成像、电子显微镜和蛋白质组学，研究人员发现，ELVA是由内溶酶体、自噬体和蛋白酶体组成的非膜结合区室，由RUFY1形成的蛋白质基质结合在一起。功能分析显示，在未成熟卵母细胞中，ELVA螯合聚集蛋白，包括TDP-43，并在卵母细胞成熟时降解它们。抑制ELVA的降解活性会导致蛋白质聚集体在胚胎中积累，对胚胎存活不利。

因此，ELVA代表了一种在长寿细胞中保护蛋白质稳态的策略。

附：英文原文

Title: Mouse oocytes sequester aggregated proteins in degradative super-organelles

Author: Gabriele Zaffagnini, Shiya Cheng, Marion C. Salzer, Barbara Pernaute, Juan Manuel Duran, Manuel Irimia, Melina Schuh, Elvan Bke

Issue&Volume: 2024-02-20

Abstract: Oocytes are among the longest-lived cells in the body and need to preserve their cytoplasm to support proper embryonic development. Protein aggregation is a major threat for intracellular homeostasis in long-lived cells. How oocytes cope with protein aggregation during their extended life is unknown. Here, we find that mouse oocytes accumulate protein aggregates in specialized compartments that we named endolysosomal vesicular assemblies (ELVAs). Combining live-cell imaging, electron microscopy, and proteomics, we found that ELVAs are non-membrane-bound compartments composed of endolysosomes, autophagosomes, and proteasomes held together by a protein matrix formed by RUFY1. Functional assays revealed that in immature oocytes, ELVAs sequester aggregated proteins, including TDP-43, and degrade them upon oocyte maturation. Inhibiting degradative activity in ELVAs leads to the accumulation of protein aggregates in the embryo and is detrimental for embryo survival. Thus, ELVAs represent a strategy to safeguard protein homeostasis in long-lived cells.

DOI: 10.1016/j.cell.2024.01.031

Source: https://www.cell.com/cell/fulltext/S0092-8674(24)00068-0