Pink1/Parkin-mediated mitophagy play a protective role in cisplatin induced renal tubular epithelial cells injury
Pink1/Parkin-mediated mitophagy play a protective role in cisplatin induced renal tubular epithelial cells injury
复制标题
Pink1/Parkin介导的线粒体自噬在顺铂诱导的肾小管上皮细胞损伤中发挥保护作用
DOI：
10.1016/j.yexcr.2016.12.015
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发表时间：
2017-01-15
影响因子：
3.7
通讯作者：
Yuan, Yanggang
中科院分区：
文献类型：
--
作者：
Zhao, Chuanyan;Chen, Zhuyun;Yuan, Yanggang
在治疗多种恶性肿瘤时，顺铂经常引起急性肾损伤 (AKI)。线粒体功能障碍是顺铂肾毒性的主要原因之一。先前的研究表明，Pink1 和 Parkin 在调节线粒体自噬中发挥核心作用，线粒体自噬是通过特异性消除功能障碍或受损线粒体的关键保护机制。然而，在顺铂诱导的肾毒性中调节线粒体自噬的机制仍有待阐明。本研究的目的是探讨Pink1/Parkin通路在顺铂治疗期间线粒体自噬、线粒体功能障碍和肾近端肾小管细胞损伤中的影响。在培养的人肾近端肾小管细胞中，我们发现Pink1/Parkin的敲低会导致线粒体功能恶化，通过抑制线粒体自噬导致细胞损伤增加。此外，Pink1/Parkin 的过度表达可通过促进线粒体自噬来防止顺铂诱导的线粒体功能障碍和细胞损伤。我们的结果提供了明确的证据，表明 Pink1/Parkin 依赖性线粒体自噬已经确定了治疗顺铂诱导的 AKI 的潜在靶点。
Cisplatin often causes acute kidney injury (AKI) in the treatment of a wide variety of malignancies. Mitochondrial dysfunction is one of the main reasons for cisplatin nephrotoxicity. Previous study showed that Pink1 and Parkin play central roles in regulating the mitophagy, which is a key protective mechanism by specifically eliminating dysfunctional or damaged mitochondria. However, the mechanisms that modulate mitophagy in cisplatin induced nephrotoxicity remain to be elucidated. The purpose of this study was to investigate the effects of Pink1/Parkin pathway in mitophagy, mitochondrial dysfunction and renal proximal tubular cells injury during cisplatin treatment. In cultured human renal proximal tubular cells, we found that knockdown of Pink1/Parkin induced the aggravation of mitochondrial function, leading to the increase of cell injury through inhibition of mitophagy. Additionally, the overexpression of Pink1/Parkin protected against cisplatin-induced mitochondrial dysfunction and cell injury by promoting mitophagy. Our results provide clear evidence that Pink1/Parkin-dependent mitophagy has identified potential targets for the treatment of cisplatin-induced AKI.