1 Division of Pulmonary and Critical Care Medicine, Weill Cornell Medicine , New York, New York.
2 Division of Nephrology and Hypertension, Joan and Sanford I. Weill Department of Medicine, Weill Cornell Medicine , New York, New York.
Antioxid Redox Signal. 2019 Jan 1;30(1):138-159. doi: 10.1089/ars.2018.7518. Epub 2018 Mar 28.
Autophagy, a lysosome-dependent homeostatic process inherent to cells and tissues, has emerging significance in the pathogenesis of human disease. This process enables the degradation and turnover of cytoplasmic substrates via membrane-dependent sequestration in autophagic vesicles (autophagosomes) and subsequent lysosomal delivery of cargo. Recent Advances: Selective forms of autophagy can target specific substrates (e.g., organelles, protein aggregates, and lipids) for processing. Autophagy is highly regulated by oxidative stress, including exposure to altered oxygen tension, by direct and indirect mechanisms, and contributes to inducible defenses against oxidative stress. Mitochondrial autophagy (mitophagy) plays a critical role in the oxidative stress response, through maintenance of mitochondrial integrity.
Autophagy can impact a number of vital cellular processes including inflammation and adaptive immunity, host defense, lipid metabolism and storage, mitochondrial homeostasis, and clearance of aggregated proteins, all which may be of significance in human disease. Autophagy can exert both maladaptive and adaptive roles in disease pathogenesis, which may also be influenced by autophagy impairment. This review highlights the essential roles of autophagy in human diseases, with a focus on diseases in which oxidative stress or inflammation play key roles, including human lung, liver, kidney and heart diseases, metabolic diseases, and diseases of the cardiovascular and neural systems.
Investigations that further elucidate the complex role of autophagy in the pathogenesis of disease will facilitate targeting this pathway for therapies in specific diseases.
自噬是一种细胞和组织中固有的溶酶体依赖性的内稳态过程，在人类疾病的发病机制中具有重要意义。这个过程通过将细胞质底物通过膜依赖性隔离在自噬小泡（自噬体）中，并随后将货物递送至溶酶体来实现降解和周转。
选择性自噬可以靶向特定的底物（例如细胞器、蛋白质聚集体和脂质）进行处理。自噬受到氧化应激的高度调节，包括通过直接和间接机制暴露于改变的氧张力，并且有助于对氧化应激的诱导防御。线粒体自噬（mitophagy）通过维持线粒体完整性，在氧化应激反应中发挥关键作用。
自噬可以影响许多重要的细胞过程，包括炎症和适应性免疫、宿主防御、脂质代谢和储存、线粒体稳态以及聚集蛋白的清除，所有这些在人类疾病中都可能具有重要意义。自噬在疾病发病机制中可以发挥适应性和非适应性作用，这也可能受到自噬损伤的影响。本综述强调了自噬在人类疾病中的重要作用，重点关注氧化应激或炎症发挥关键作用的疾病，包括人类肺部、肝脏、肾脏和心脏疾病、代谢疾病以及心血管和神经系统疾病。
进一步阐明自噬在疾病发病机制中的复杂作用的研究将有助于针对特定疾病靶向该途径进行治疗。
