Triggering of Parkin Mitochondrial Translocation in Mitophagy: Implications for Liver Diseases.
Triggering of Parkin Mitochondrial Translocation in Mitophagy: Implications for Liver Diseases.
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DOI：
10.3389/fphar.2016.00100
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发表时间：
2016
影响因子：
5.6
通讯作者：
Otsuki Y
中科院分区：
文献类型：
--
作者：
Eid N;Ito Y;Otsuki Y
越来越多的体外研究证据表明，线粒体自噬（受损线粒体的选择性自噬清除）是一种与细胞暴露于各种线粒体应激源相关的促生存机制。最近，数量有限的关于酒精性脂肪肝动物模型的出版物报道，Parkin 介导的线粒体自噬可以减轻肝细胞凋亡，改善线粒体质量并抑制脂肪变性（脂质积累）。从这个角度来看，作者重点关注 Parkin 线粒体易位的机制（线粒体自噬激活的一个关键考虑因素）以及线粒体自噬在肝病中的治疗意义。还简要讨论了 DNA 修复和 Parkin 除了线粒体自噬之外的其他功能。该论文还显示了作者当前研究的原始数据，表明乙醇处理的大鼠的肝脏线粒体自噬增强，这与线粒体 DNA 氧化损伤引发的 Parkin 线粒体易位有关。可能触发肝细胞中 Parkin 线粒体易位和/或抑制此类易位阻遏物的天然或药物产品可能是酒精性和非酒精性脂肪肝疾病的潜在治疗靶点。
A growing body of evidence based on in vitro studies indicates that mitophagy (selective autophagic clearance of damaged mitochondria) is a prosurvival mechanism associated with cellular exposure to various mitochondrial stressors. Very recently, a limited number of publications on animal-based models of alcoholic fatty liver diseases have reported that Parkin-mediated mitophagy may mitigate hepatocyte apoptosis, improve mitochondrial quality and suppress steatosis (lipid accumulation). From this perspective, the authors focus on the mechanisms of Parkin mitochondrial translocation (a key consideration in mitophagy activation) and therapeutic implications of mitophagy in liver disease. DNA repair and other functions of Parkin beyond mitophagy are also briefly discussed. The paper additionally shows original data from the authors’ current research indicating enhanced hepatic mitophagy in ethanol-treated rats, which is associated with Parkin mitochondrial translocation triggered by oxidative mitochondrial DNA damage. Natural or pharmaceutical products that may trigger Parkin mitochondrial translocation in hepatocytes and/or suppress repressors of such translocation could be a potential therapeutic target in alcoholic and non-alcoholic fatty liver disease.