ABSTRACT

Selective autophagy is a specific elimination of certain intracellular substrates by autophagic pathways. The most studied macroautophagy pathway involves tagging and recognition of a specific cargo by the autophagic membrane (phagophore) followed by the complete sequestration of targeted cargo from the cytosol by the double-membrane vesicle, autophagosome. Until recently, the knowledge about selective macroautophagy was minimal, but now there is a panoply of links elucidating how phagophores engulf their substrates selectively. The studies of selective autophagy processes have further stressed the importance of using the in vivo models to validate new in vitro findings and discover the physiologically relevant mechanisms. However, dissecting how the selective autophagy occurs yet remains difficult in living organisms, because most of the organelles are relatively inaccessible to observation and experimental manipulation in mammals. In recent years, zebrafish (Danio rerio) is widely recognized as an excellent model for studying autophagic processes in vivo because of its optical accessibility, genetic manipulability and translational potential. Several selective autophagy pathways, such as mitophagy, xenophagy, lipophagy and aggrephagy, have been investigated using zebrafish and still need to be studied further, while other selective autophagy pathways, such as pexophagy or reticulophagy, could also benefit from the use of the zebrafish model. In this review, we shed light on how zebrafish contributed to our understanding of these selective autophagy processes by providing the in vivo platform to study them at the organismal level and highlighted the versatility of zebrafish model in the selective autophagy field.

Abbreviations: AD: Alzheimer disease; ALS: amyotrophic lateral sclerosis; Atg: autophagy-related; CMA: chaperone-mediated autophagy; CQ: chloroquine; HsAMBRA1: human AMBRA1; KD: knockdown; KO: knockout; LD: lipid droplet; MMA: methylmalonic acidemia; PD: Parkinson disease; Tg: transgenic.

摘要

选择性自噬是通过自噬途径特异性消除某些细胞内底物。研究最多的巨自噬途径涉及通过自噬膜（吞噬细胞）标记和识别特定货物，然后通过双膜囊泡（自噬体）将目标货物从细胞质中完全隔离。直到最近，关于选择性巨自噬的知识还很少，但现在有大量的链接阐明了吞噬细胞如何选择性地吞噬其底物。选择性自噬过程的研究进一步强调了使用体内模型来验证新的体外发现并发现生理相关机制的重要性。然而，剖析选择性自噬如何在生物体中发生仍然很困难，因为大多数细胞器相对难以在哺乳动物中观察和实验操作。近年来，斑马鱼（Danio rerio ）因其光学可及性、遗传可操作性和转化潜力而被广泛认为是研究体内自噬过程的优秀模型。几种选择性自噬途径，如线粒体自噬、异体自噬、脂肪自噬和聚合自噬，已经使用斑马鱼进行了研究，但仍需要进一步研究，而其他选择性自噬途径，如 pexophagy 或网状自噬，也可以从斑马鱼模型的使用中受益。在这篇综述中，我们阐明了斑马鱼如何通过提供在有机体水平上研究这些选择性自噬过程的体内平台来促进我们对这些选择性自噬过程的理解，并强调了斑马鱼模型在选择性自噬领域的多功能性。

缩写： AD：阿尔茨海默病；ALS：肌萎缩侧索硬化症；Atg：自噬相关；CMA：分子伴侣介导的自噬；CQ：氯喹；HsAMBRA1：人 AMBRA1；KD：击倒；KO：淘汰赛；LD：脂滴；MMA：甲基丙二酸血症；PD：帕金森病；Tg：转基因。