Laboratory of Signaling and Pathogenesis, Institut Pasteur, CNRS UMR3691, Paris, France.
Front Immunol. 2018 Jun 19;9:1243. doi: 10.3389/fimmu.2018.01243. eCollection 2018.
Optineurin (Optn) is a 577 aa protein encoded by the gene. Mutations of are associated with normal tension glaucoma and amyotrophic lateral sclerosis, and its gene has also been linked to the development of Paget's disease of bone and Crohn's disease. Optn is involved in diverse cellular functions, including NF-κB regulation, membrane trafficking, exocytosis, vesicle transport, reorganization of actin and microtubules, cell cycle control, and autophagy. Besides its role in xenophagy and autophagy of aggregates, Optn has been identified as a primary autophagy receptor, among the five adaptors that translocate to mitochondria during mitophagy. Mitophagy is a selective macroautophagy process during which irreparable mitochondria are degraded, preventing accumulation of defective mitochondria and limiting the release of reactive oxygen species and proapoptotic factors. Mitochondrial quality control mitophagy is central to the health of cells. One of the important surveillance pathways of mitochondrial health is the recently defined signal transduction pathway involving the mitochondrial PTEN-induced putative kinase 1 (PINK1) protein and the cytosolic RING-between-RING ubiquitin ligase Parkin. Both of these proteins, when mutated, have been identified in certain forms of Parkinson's disease. By targeting ubiquitinated mitochondria to autophagosomes through its association with autophagy related proteins, Optn is responsible for a critical step in mitophagy. This review reports recent discoveries on the role of Optn in mitophagy and provides insight into its link with neurodegenerative diseases. We will also discuss the involvement of Optn in other pathologies in which mitophagy dysfunctions are involved including cancer.
视神经萎缩症相关蛋白（Optn）是一种由 OPTN 基因编码的 577 个氨基酸的蛋白质。该基因突变与正常眼压型青光眼和肌萎缩性侧索硬化症有关，其基因也与骨 Paget 病和克罗恩病的发展有关。Optn 参与多种细胞功能，包括 NF-κB 调节、膜运输、胞吐作用、囊泡运输、肌动蛋白和微管的重排、细胞周期控制和自噬。除了在异噬体和聚集体的自噬中的作用外，Optn 已被确定为主要的自噬受体之一，在参与线粒体自噬时，有五个衔接蛋白向线粒体转移。线粒体自噬是一种选择性的巨自噬过程，在此过程中，不可修复的线粒体被降解，防止缺陷线粒体的积累，并限制活性氧物质和促凋亡因子的释放。线粒体质量控制和线粒体自噬对于细胞的健康至关重要。线粒体健康的一个重要监测途径是最近定义的信号转导途径，涉及线粒体 PTEN 诱导的假定激酶 1（PINK1）蛋白和细胞质环间环泛素连接酶 Parkin。这两种蛋白质，当发生突变时，已经在某些形式的帕金森病中被发现。通过与自噬相关蛋白结合，将泛素化的线粒体靶向自噬体，Optn 负责线粒体自噬的一个关键步骤。本综述报告了 Optn 在线粒体自噬中的作用的最新发现，并深入了解了其与神经退行性疾病的联系。我们还将讨论 Optn 在其他涉及线粒体自噬功能障碍的病理学中的参与，包括癌症。
