2. Academic Validation
  3. Gefitinib facilitates PINK1/Parkin-mediated mitophagy by enhancing mitochondrial recruitment of OPTN

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

  • Fundam Res. 2022 Mar 3;2(5):807-816. doi: 10.1016/j.fmre.2021.12.017.
Ningning Li 1,  Shan Sun 1,  Guoqiang Ma 1,  Hongyu Hou 1,  Qilian Ma 1,  Li Zhang 2,  Zengli Zhang 3,  Hongfeng Wang 1,  Zheng Ying 1
Affiliations

Affiliations

  • 1 Jiangsu Key Laboratory of Neuropsychiatric Diseases and College of Pharmaceutical Sciences, Soochow University, Suzhou, Jiangsu 215123, China.
  • 2 Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi, Jiangsu 214063, China.
  • 3 Department of Respiratory and Critical Care Medicine, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215004, China.
PMID: 38933121 DOI: 10.1016/j.fmre.2021.12.017
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.

Keywords

Autophagy; Gefitinib; Mitophagy; OPTN; Parkin.

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