Department of Physiology and Pathophysiology, Peking University Health Science Center, Beijing, China.
Adv Exp Med Biol. 2021;1208:67-77. doi: 10.1007/978-981-16-2830-6_5.
Autophagy is a major intracellular degradation/recycling system that ubiquitously exists in eukaryotic cells. Autophagy contributes to the turnover of cellular components through engulfing portions of the cytoplasm or organelles and delivering them to the lysosomes/vacuole to be degraded. The trafficking of autophagosomes and their fusion with lysosomes are important steps that complete their maturation and degradation. In cells such as neuron, autophagosomes traffic long distances along the axon, while in other specialized cells such as cardiomyocytes, it is unclear how and even whether autophagosomes are transported. Therefore, it is important to learn more about the processes and mechanisms of autophagosome trafficking to lysosomes/vacuole during autophagy. The mechanisms of autophagosome trafficking are similar to those of other organelles trafficking within cells. The machinery mainly includes cytoskeletal systems such as actin and microtubules, motor proteins such as myosins and the dynein-dynactin complex, and other proteins like LC3 on the membrane of autophagosomes. Factors regulating autophagosome trafficking have not been widely studied. To date the main reagents identified for disrupting autophagosome trafficking include: 1. Microtubule polymerization reagents, which disrupt microtubules by interfering with microtubule dynamics, thus directly influence microtubule-dependent autophagosome trafficking 2. F-actin-depolymerizing drugs, which inhibit autophagosome formation, and also subsequently inhibit autophagosome trafficking 3. Motor protein regulators, which directly affect autophagosome trafficking.
自噬是一种普遍存在于真核细胞中的主要细胞内降解/回收系统。自噬通过吞噬细胞质或细胞器的部分内容,并将其递送至溶酶体/液泡进行降解,从而促进细胞成分的更新。自噬体的运输及其与溶酶体的融合是完成其成熟和降解的重要步骤。在神经元等细胞中,自噬体沿着轴突长距离运输,而在其他特化细胞如心肌细胞中,自噬体如何运输甚至是否运输尚不清楚。因此,了解更多关于自噬过程中自噬体向溶酶体/液泡运输的过程和机制非常重要。自噬体运输的机制与细胞内其他细胞器的运输机制相似。该机制主要包括细胞骨架系统,如肌动蛋白和微管,肌球蛋白和动力蛋白-动力蛋白复合物等马达蛋白,以及自噬体膜上的 LC3 等其他蛋白。自噬体运输的调节因子尚未得到广泛研究。迄今为止,已确定的主要用于破坏自噬体运输的试剂包括:1. 微管聚合试剂,通过干扰微管动力学来破坏微管,从而直接影响微管依赖性自噬体运输;2. F-肌动蛋白解聚药物,抑制自噬体的形成,也随后抑制自噬体的运输;3. 马达蛋白调节剂,直接影响自噬体的运输。