Gefitinib facilitates PINK1/Parkin-mediated mitophagy by enhancing mitochondrial recruitment of OPTN  

作　　者：Ningning Li Shan Sun Guoqiang Ma Hongyu Hou Qilian Ma Li Zhang Zengli Zhang Hongfeng Wang Zheng Ying 

机构地区：[1]Jiangsu Key Laboratory of Neuropsychiatric Diseases and College of Pharmaceutical Sciences,Soochow University,Suzhou,Jiangsu 215123,China [2]Department of Respiratory and Critical Care Medicine,The Second Affiliated Hospital of Soochow University,Suzhou,Jiangsu 215004,China [3]Key Laboratory of Nuclear Medicine,Ministry of Health,Jiangsu Key Laboratory of Molecular Nuclear Medicine,Jiangsu Institute of Nuclear Medicine,Wuxi,Jiangsu 214063,China

出　　处：《Fundamental Research》2022年第5期807-816,共10页自然科学基础研究（英文版）

基　　金：supported by the National Natural Science Foundation of China(Grant Nos.82022022,31771117,and 82071274);a Project Funded by the Suzhou Science and Technology Program(Grant No.SYS2019068);a Project Funded by the Clinical Research Program of the WuJieping Medical Foundation(Grant No.320.6750.19092-32);a Project Funded by Jiangsu Key Laboratory of Neuropsychiatric Diseases(Grant No.BM2013003);a Project Funded by the Priority Academic Program Development of the Jiangsu Higher Education Institutes(PAPD).

摘　　要：Gefitinib,a well-known epidermal growth factor receptor(EGFR)tyrosine kinase inhibitor for the targeted therapy of lung cancer,induces autophagy in association with drug resistance.However,it remains unclear whether gefitinib treatment can affect the selective form of autophagy(i.e.,mitophagy)and be beneficial for the treatment of human diseases with decreased autophagy,such as neurodegenerative diseases.Here,we show that gefitinib treatment promotes PINK1/Parkin-mediated mitophagy in both nonneuronal and neuronal cells,and this effect is independent of EGFR.Moreover,we found that gefitinib treatment increases the recruitment of the autophagy receptor optineurin(OPTN)to damaged mitochondria,which is a downstream signaling event in PINK1/Parkin-mediated mitophagy.In addition,gefitinib treatment significantly alleviated neuronal damage in TBK1-deficient neurons,resulting in impeded mitophagy.In conclusion,our study suggests that gefitinib promotes PINK1/Parkin-mediated mitophagy via OPTN and may be beneficial for the treatment of neurodegenerative diseases that are associated with defective mitophagy.

关 键 词：GEFITINIB Autophagy MITOPHAGY PARKIN OPTN 

分 类 号：R94[医药卫生—药剂学]