Department of Biomedical Sciences of Cells and Systems, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Department of Biomedical Sciences of Cells and Systems, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands; School of Medicine and Health Sciences, Carl von Ossietzky University Oldenburg, Oldenburg, Germany.
Trends Biochem Sci. 2023 Mar;48(3):216-228. doi: 10.1016/j.tibs.2022.09.012. Epub 2022 Oct 21.
Aggrephagy describes the selective lysosomal transport and turnover of cytoplasmic protein aggregates by macro-autophagy. In this process, protein aggregates and conglomerates are polyubiquitinated and then sequestered by autophagosomes. Soluble selective autophagy receptors (SARs) are central to aggrephagy and physically bind to both ubiquitin and the autophagy machinery, thus linking the cargo to the forming autophagosomal membrane. Because the accumulation of protein aggregates is associated with cytotoxicity in several diseases, a better molecular understanding of aggrephagy might provide a conceptual framework to develop therapeutic strategies aimed at delaying the onset of these pathologies by preventing the buildup of potentially toxic aggregates. We review recent advances in our knowledge about the mechanism of aggrephagy.
聚集体自噬描述了通过巨自噬选择性溶酶体运输和转化细胞质蛋白聚集体的过程。在这个过程中，蛋白聚集体和凝聚体被多泛素化，然后被自噬体隔离。可溶性选择性自噬受体 (SARs) 是聚集体自噬的核心，它们与泛素和自噬机制都有物理结合，从而将货物与正在形成的自噬体膜连接起来。由于在几种疾病中，蛋白聚集体的积累与细胞毒性有关，因此更好地了解聚集体自噬的分子机制可能为开发治疗策略提供一个概念框架，通过防止潜在毒性聚集体的积累来延迟这些病理的发生。我们综述了关于聚集体自噬机制的最新进展。
