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Title: PINK1/Parkin-mediated mitophagy promotes resistance to sonodynamic therapy
Authors: Song, L 
Huang, YM 
Hou, XD 
Yang, YH 
Kala, S 
Qiu, ZH 
Zhang, R 
Sun, L 
Issue Date: 2018
Source: Cellular physiology and biochemistry, 2018, v. 49, no. 5, p. 1825-1839
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-SDTinduced cell death in MCF-7 cells.
Keywords: Sonodynamic therapy
Mitophagy
ROS
Mitochondrial dynamics
PINK1/Parkin signaling pathway
Publisher: Karger
Journal: Cellular physiology and biochemistry 
ISSN: 1015-8987
EISSN: 1421-9778
DOI: 10.1159/000493629
Rights: 2018 The Author(s)
This article is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND) (http://www.karger.com/Services/OpenAccessLicense). Usage and distribution for commercial purposes as well as any distribution of modified material requires written permission.
The following publication Song, L., Huang, Y.M., Hou, X.D., Yang, Y.H., Kala, S., Qiu, Z.H., ... & Sun, L. (2018). PINK1/Parkin-mediated mitophagy promotes resistance to sonodynamic therapy. Cellular physiology and biochemistry, 49 (5), 1825-1839 is available at https://dx.doi.org/10.1159/000493629
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