Role of autophagy in alcohol and drug-induced liver injury.
Role of autophagy in alcohol and drug-induced liver injury.
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DOI：
10.1016/j.fct.2019.111075
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发表时间：
2019-12
期刊：
影响因子：
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通讯作者：
Jessica A. Williams;W. Ding
中科院分区：
文献类型：
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作者：
Jessica A. Williams;W. Ding
酒精相关性肝病（ALD）和药物性肝损伤（DILI）是严重肝病的常见原因，缺乏成功的治疗方法。自噬通过选择性去除肝细胞中受损的线粒体（线粒体自噬）、脂滴（脂肪自噬）、蛋白质聚集体和加合物，在酒精性肝脏疾病和肝性肝脏疾病中发挥保护作用。自噬还通过降解干扰素调节因子1（IRF1）和肝巨噬细胞中受损的线粒体来保护免受ALD。具体来说，我们将讨论选择性自噬去除受损的线粒体和脂滴在肝细胞和自噬介导的降解IRF1在肝巨噬细胞作为保护机制，对酒精诱导的肝损伤和脂肪变性。此外，选择性自噬去除受损的线粒体和蛋白加合物，保护对DILI的讨论。ALD和DILI的新疗法的开发是非常必要的，选择性自噬途径可能提供有前途的目标。药物和酒精对自噬调节的影响以及自噬对DILI和ALD的保护机制在这篇综述中被强调。
Alcohol-related liver disease (ALD) and drug-induced liver injury (DILI) are common causes of severe liver disease, and successful treatments are lacking. Autophagy plays a protective role in both ALD and DILI by selectively removing damaged mitochondria (mitophagy), lipid droplets (lipophagy), protein aggregates and adducts in hepatocytes. Autophagy also protects against ALD by degrading interferon regulatory factor 1 (IRF1) and damaged mitochondria in hepatic macrophages. Specifically, we will discuss selective autophagy for removal of damaged mitochondria and lipid droplets in hepatocytes and autophagy-mediated degradation of IRF1 in hepatic macrophages as protective mechanisms against alcohol-induced liver injury and steatosis. In addition, selective autophagy for removal of damaged mitochondria and protein adducts for protection against DILI is discussed in this review. Development of new therapeutics for ALD and DILI is greatly needed, and selective autophagy pathways may provide promising targets. Drug and alcohol effects on autophagy regulation as well as protective mechanisms of autophagy against DILI and ALD are highlighted in this review.