Targeting Pink1-Parkin-mediated mitophagy for treating liver injury.
Targeting Pink1-Parkin-mediated mitophagy for treating liver injury.
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DOI：
10.1016/j.phrs.2015.09.020
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发表时间：
2015-12
影响因子：
9.3
通讯作者：
Ding WX
中科院分区：
文献类型：
--
作者：
Williams JA;Ding WX
酒精性肝病和对乙酰氨基酚过量是美国严重肝病和肝功能衰竭的常见原因，且无法治愈。因此，需要开发新的治疗策略来治疗对乙酰氨基酚和酒精引起的肝损伤。我们证明，自噬通过线粒体自噬去除受损的线粒体，从而防止酒精和对乙酰氨基酚引起的肝损伤，线粒体自噬是一种选择性形式的自噬，特异性降解受损线粒体。众所周知，Parkin 是体外模型中诱导线粒体自噬所必需的，我们之前表明 Parkin 介导的线粒体自噬途径可能对酒精和对乙酰氨基酚引起的肝损伤发挥保护作用。因此，药物上调肝脏中 Parkin 介导的线粒体自噬途径可能为治疗对乙酰氨基酚和酒精引起的肝损伤提供一种新颖且有效的治疗选择。在这篇综述中，我们讨论了 Parkin 介导的线粒体自噬的调节以及干预该途径的可能治疗目标。
Alcoholic liver disease and acetaminophen overdose are common causes of severe liver disease and liver failure in the United States for which there is no cure. Therefore, development of new therapeutic strategies for treatment of liver injury caused by acetaminophen and alcohol is needed. We demonstrated that autophagy protects against alcohol and acetaminophen-induced liver injuries by removing damaged mitochondria via mitophagy, which is a selective form of autophagy specific for degradation of damaged mitochondria. Parkin is well-known to be required for mitophagy induction in in vitro models, and we previously showed that the Parkin-mediated mitophagy pathway likely plays a protective role against alcohol and acetaminophen-induced liver injuries. Therefore, pharmacological upregulation of the Parkin-mediated mitophagy pathway in the liver may provide a novel and effective therapeutic option for treatment of acetaminophen and alcohol-induced liver injuries. In this review, we discuss regulation of Parkin-mediated mitophagy and possible therapeutic targets of intervention in this pathway.