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

被引:63
作者
Arena, Giuseppe [1 ,2 ,3 ,4 ]
Valente, Enza Maria [5 ,6 ]
机构
[1] IRCM, Montpellier, France
[2] INSERM, U1194, Montpellier, France
[3] Univ Montpellier, Montpellier, France
[4] Inst Reg Canc Montpellier, Montpellier, France
[5] Univ Salerno, Dept Med & Surg, Sect Neurosci, Salerno, Italy
[6] IRCCS, Santa Lucia Fdn, Neurogenet Unit, Via Fosso di Fiorano, Rome, Italy
关键词
PINK1; Parkinson disease; neurodegeneration; cancer; serine-threonine kinase; mitochondria; autophagy; mitophagy; COMPLEX I ACTIVITY; PARKINSONS-DISEASE; MITOCHONDRIAL DYSFUNCTION; OXIDATIVE STRESS; ALPHA-SYNUCLEIN; SELECTIVE AUTOPHAGY; CATALYTIC-ACTIVITY; DOWN-REGULATION; MITOPHAGY; PHOSPHORYLATION;
D O I
10.1002/path.4815
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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 (C) 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
引用
收藏
页码:251 / 263
页数:13
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