线粒体激酶PINK1的功能及其在神经退行性疾病与肿瘤中作用的研究进展

Function of mitochondrial kinase PINK1 and the study progress in neurodegenerative diseases and cancer

关键词:  PINK1  线粒体质量控制  神经退行性疾病  肿瘤

Key words:  PINK1  mitochondrial quality control  neurodegenerative diseases  cancer

摘要:

PINK1是一种线粒体丝苏氨酸蛋白激酶，其在氧化应激诱导的线粒体功能失调中起保护性作用。线粒体膜电位去极化时，PINK1募集parkin蛋白诱导线粒体自噬。生理状态下，PINK1在线粒体中被剪切并释放入胞质促进神经元分化。PINK1突变能够导致常染色体隐性早发帕金森病。在非神经退行性疾病中，PINK1通过激活胞质AKT信号通路、与线粒体抗凋亡蛋白Bcl-XL相互作用等机制，调节神经胶质瘤、乳腺癌等肿瘤细胞的生长与凋亡。本文对PINK1的生理功能及其在神经退行性疾病和肿瘤发生过程中的作用进行综述。

Abstract:

PTEN-induced kinase 1 (PINK1) is a mitochondria targeted serine/threonine kinase, which protects cells against stress-induced mitochondrial dysfunction. PINK1 activity causes the parkin protein to bind to depolarized mitochondria and induces autophagy of the mitochondria. PINK1 is processed by healthy mitochondria and released to trigger neuron differentiation. Its mutations cause one form of autosomal recessive early-onset Parkinson's disease. In addition, PINK1 can regulate growth and apoptosis of tumor cells such as gliocytoma and breast cancer via activation of AKT signaling or interaction with anti-apoptotic protein Bcl-XL in non-neurodegenerative disease.This review summarizes the physiological roles of PINK1 and the mechanisms in the pathogenesis of neurodegenerative disease and cancer.