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Role of autophagy in alcohol and drug-induced liver injury.
Food and Chemical Toxicology ( IF 3.9 ) Pub Date : 2019-12-23 , DOI: 10.1016/j.fct.2019.111075 Jessica A Williams 1 , Wen-Xing Ding 1
Food and Chemical Toxicology ( IF 3.9 ) Pub Date : 2019-12-23 , DOI: 10.1016/j.fct.2019.111075 Jessica A Williams 1 , Wen-Xing Ding 1
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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.
中文翻译：
自噬在酒精和药物性肝损伤中的作用。
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，目前尚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），脂质滴（脂噬体），蛋白质聚集体和加合物，在ALD和DILI中均起保护作用。自噬还可以通过降解干扰素调节因子1（IRF1）和肝巨噬细胞中的线粒体受损来预防ALD。具体来说，我们将讨论选择性自噬以去除肝细胞中受损的线粒体和脂质滴以及在肝巨噬细胞中自噬介导的IRF1降解，作为针对酒精诱导的肝损伤和脂肪变性的保护机制。此外，在这篇综述中讨论了选择性自噬以去除受损的线粒体和蛋白质加合物以抵抗DILI。迫切需要开发针对ALD和DILI的新疗法，选择性自噬途径可能会提供有希望的靶标。本文综述了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。
更新日期：2019-12-23
中文翻译：
自噬在酒精和药物性肝损伤中的作用。
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，目前尚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），脂质滴（脂噬体），蛋白质聚集体和加合物，在ALD和DILI中均起保护作用。自噬还可以通过降解干扰素调节因子1（IRF1）和肝巨噬细胞中的线粒体受损来预防ALD。具体来说，我们将讨论选择性自噬以去除肝细胞中受损的线粒体和脂质滴以及在肝巨噬细胞中自噬介导的IRF1降解，作为针对酒精诱导的肝损伤和脂肪变性的保护机制。此外，在这篇综述中讨论了选择性自噬以去除受损的线粒体和蛋白质加合物以抵抗DILI。迫切需要开发针对ALD和DILI的新疗法，选择性自噬途径可能会提供有希望的靶标。本文综述了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。
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