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PINK1 成为焦点:一种多功能的兼性蛋白在人类健康和疾病中的作用。

PINK1 in the limelight: multiple functions of an eclectic protein in human health and disease.

机构信息

Institut de Recherche en Cancérologie de Montpellier (IRCM), Montpellier, France.

INSERM, U1194, Montpellier, France.

出版信息

J Pathol. 2017 Jan;241(2):251-263. doi: 10.1002/path.4815. Epub 2016 Nov 12.

Abstract

The gene PINK1 [phosphatase and tensin homologue (PTEN)-induced putative kinase 1] encodes a serine/threonine kinase which was initially linked to the pathogenesis of a familial form of Parkinson's disease. Research on PINK1 has recently unravelled that its multiple functions extend well beyond neuroprotection, implicating this eclectic protein in a growing number of human pathologies, including cancer, diabetes, cardiopulmonary dysfunctions, and inflammation. Extensive studies have identified PINK1 as a crucial player in the mitochondrial quality control pathway, required to label damaged mitochondria and promote their elimination through an autophagic process (mitophagy). Mounting evidence now indicates that PINK1 activities are not restricted solely to mitophagy, and that different subcellular and even sub-mitochondrial pools of PINK1 are involved in distinct signalling cascades to regulate cell metabolism and survival. In this review, we provide a concise overview on the different functions of PINK1 and their potential role in human diseases. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

摘要

PINK1 [磷酸酶和张力蛋白同源物(PTEN)诱导的假定激酶 1] 基因编码一种丝氨酸/苏氨酸激酶,最初与家族性帕金森病的发病机制有关。对 PINK1 的研究最近揭示了其多种功能远不止于神经保护,这表明这种折衷蛋白与越来越多的人类疾病有关,包括癌症、糖尿病、心肺功能障碍和炎症。广泛的研究已经确定 PINK1 是线粒体质量控制途径中的关键参与者,它需要标记受损的线粒体,并通过自噬过程(mitophagy)促进其清除。越来越多的证据表明,PINK1 的活性不仅限于 mitophagy,不同的亚细胞甚至线粒体亚区的 PINK1 参与不同的信号级联反应,以调节细胞代谢和存活。在这篇综述中,我们简要概述了 PINK1 的不同功能及其在人类疾病中的潜在作用。版权所有 © 2016 英国和爱尔兰病理学会。由 John Wiley & Sons,Ltd. 出版。

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