Gefitinib Facilitates PINK1/Parkin-mediated Mitophagy by Enhancing Mitochondrial Recruitment of OPTN

Overview

Journal Fundam Res

Date 2024 Jun 27

PMID 38933121

Authors

Ningning Li

Shan Sun

Guoqiang Ma

Hongyu Hou

Qilian Ma

Li Zhang

Zengli Zhang

Hongfeng Wang

Zheng Ying

Affiliations

Soon will be listed here.

Abstract

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.

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