Center for Drug Safety Evaluation and Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China.
Institute of Pharmacology & Toxicology, Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China.
Autophagy. 2022 Jan;18(1):73-85. doi: 10.1080/15548627.2021.1908722. Epub 2021 Apr 13.
Macroautophagy/autophagy is a highly conserved process in eukaryotic cells. It plays a critical role in cellular homeostasis by delivering cytoplasmic cargos to lysosomes for selective degradation. OPTN (optineurin), a well-recognized autophagy receptor, has received considerable attention due to its multiple roles in the autophagic process. OPTN is associated with many human disorders that are closely related to autophagy, such as rheumatoid arthritis, osteoporosis, and nephropathy. Here, we review the function of OPTN as an autophagy receptor at different stages of autophagy, focusing on cargo recognition, autophagosome formation, autophagosome maturation, and lysosomal quality control. OPTN tends to be protective in most autophagy associated diseases, though the molecular mechanism of OPTN regulation in these diseases is not well understood. A comprehensive review of the function of OPTN in autophagy provides valuable insight into the pathogenesis of human diseases related to OPTN and facilitates the discovery of potential key regulators and novel therapeutic targets for disease intervention in patients with autophagic diseases.: ATG: autophagy-related; APAP: acetaminophen; CALCOCO2/NDP52: calcium binding and coiled-coil domain 2; CC: coiled-coil; HACE1: HECT domain and ankyrin repeat containing E3 ubiquitin protein ligase 1; MYO6: myosin VI; IKBKG/NEMO: inhibitor of nuclear factor kappa B kinase regulatory subunit gamma; IKK: IκB kinase; LIR: LC3-interacting region; LZ: leucine zipper; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; NFKB/NF-κB: nuclear factor kappa B subunit; OPTN: optineurin; PIK3C3: phosphatidylinositol 3-kinase catalytic subunit type 3; PINK1: PTEN induced kinase 1; PRKN: parkin RBR E3 ubiquitin protein ligase; RTECs: renal tubular epithelial cells; SQSTM1/p62: sequestosome 1; TBK1: TANK binding kinase 1; TOM1: target of myb1 membrane trafficking protein; UBD: ubiquitin-binding domain; ULK1: unc-51 like autophagy activating kinase 1; WIPI2: WD repeat domain, phosphoinositide interacting 2; ZF: zinc finger.
自噬是真核细胞中一种高度保守的过程。它通过将细胞质 cargo 递送至溶酶体进行选择性降解，在细胞内稳态中发挥关键作用。OPTN（optineurin）是一种公认的自噬受体，由于其在自噬过程中的多种作用而受到广泛关注。OPTN 与许多与自噬密切相关的人类疾病有关，如类风湿性关节炎、骨质疏松症和肾病。在这里，我们综述了 OPTN 作为自噬受体在自噬不同阶段的功能，重点介绍了 cargo 识别、自噬体形成、自噬体成熟和溶酶体质量控制。尽管 OPTN 在这些疾病中的调节分子机制尚不清楚，但 OPTN 在大多数与自噬相关的疾病中趋于具有保护作用。全面综述 OPTN 在自噬中的功能，为理解与 OPTN 相关的人类疾病的发病机制提供了有价值的见解，并有助于发现自噬疾病患者疾病干预的潜在关键调节剂和新的治疗靶点。：ATG：自噬相关；APAP：对乙酰氨基酚；CALCOCO2/NDP52：钙结合和卷曲螺旋域 2；CC：卷曲螺旋；HACE1：HECT 结构域和含锚蛋白重复的 E3 泛素蛋白连接酶 1；MYO6：肌球蛋白 VI；IKBKG/NEMO：核因子 kappa B 激酶调节亚基 gamma；IKK：IκB 激酶；LIR：LC3 相互作用区域；LZ：亮氨酸拉链；MAP1LC3/LC3：微管相关蛋白 1 轻链 3；NFKB/NF-κB：核因子 kappa B 亚单位；OPTN：optineurin；PIK3C3：磷脂酰肌醇 3-激酶催化亚单位 3；PINK1：PTEN 诱导的激酶 1；PRKN：parkin RBR E3 泛素蛋白连接酶；RTECs：肾小管上皮细胞；SQSTM1/p62：自噬相关蛋白 1；TBK1：TANK 结合激酶 1；TOM1：myb1 膜转运蛋白的靶标；UBD：泛素结合域；ULK1：unc-51 样自噬激活激酶 1；WIPI2：WD 重复域、磷酸肌醇相互作用 2；ZF：锌指。
