PINK1/Parkin-Mediated Mitophagy Promotes Resistance to Sonodynamic Therapy

Lin Song, Yongmin Huang, Xuandi Hou, Yaoheng Yang, Shashwati Kala, Zhihai Qiu, Rui Zhang, Lei Sun

Research output: Journal article publicationJournal articleAcademic researchpeer-review

9 Citations (Scopus)

Abstract

Background/Aims: Sonodynamic therapy (SDT), based on the synergistic effect of low-intensity ultrasound and sonosensitizer, is a potential approach for non-invasive treatment of cancers. In SDT, mitochondria played a crucial role in cell fate determination. However, mitochondrial activities and their response to SDT remain elusive. The purpose of this study was to examine the response of mitochondria to SDT in tumor cells. Methods: A human breast adenocarcinoma cell line-MCF-7 cells were subjected to 5-aminolevulinic acid (ALA)-SDT, with an average ultrasonic intensity of 0.25W/cm 2 . Mitochondrial dynamics and redox balance were examined by confocal immunofluorescence microscopy and western blot. The occurrence of mitophagy was determined by confocal immunofluorescence microscopy. Results: Our results showed that ALA-SDT could induce mitochondrial dysfunction through mitochondrial depolarization and fragmentation and lead to mitophagy. The Parkin-dependent signaling pathway was involved and promoted resistance to ALA-SDT induced cell death. Finally, excessive production of ROS was found to be necessary for the initiation of mitophagy. Conclusion: Taken together, we conclude that ROS produced by 5-ALA-SDT could initiate PINK1/Parkin-mediated mitophagy which may exert a protective effect against 5-ALA-SDT-induced cell death in MCF-7 cells.

Original languageEnglish
Pages (from-to)1825-1839
Number of pages15
JournalCellular Physiology and Biochemistry
Volume49
Issue number5
DOIs
Publication statusPublished - 1 Oct 2018

Keywords

  • Sonodynamic therapy • Mitophagy • ROS • Mitochondrial dynamics • PINK1/Parkin signaling pathway

ASJC Scopus subject areas

  • Physiology

Cite this