Blocking exosomal secretion aggravates 1,4-benzoquinone-induced mitochondrial fission activated by the AMPK/MFF/Drp1 pathway in HL-60 cells
Fangfang Lu
Department of Preventive Medicine, School of Public Health and Management, Wenzhou Medical University, Zhejiang, China
Search for more papers by this authorQianqian Zhang
Department of Preventive Medicine, School of Public Health and Management, Wenzhou Medical University, Zhejiang, China
Department of Pharmacology, School of Pharmacy, Qilu Medical University, Shandong, China
Search for more papers by this authorMengyan Zhang
Department of Preventive Medicine, School of Public Health and Management, Wenzhou Medical University, Zhejiang, China
Search for more papers by this authorShuqiang Sun
Department of Preventive Medicine, School of Public Health and Management, Wenzhou Medical University, Zhejiang, China
Search for more papers by this authorXinjun Yang
Department of Preventive Medicine, School of Public Health and Management, Wenzhou Medical University, Zhejiang, China
Search for more papers by this authorCorresponding Author
Hongtao Yan
Department of Preventive Medicine, School of Public Health and Management, Wenzhou Medical University, Zhejiang, China
Correspondence
Hongtao Yan, Department of Preventive Medicine, School of Public Health and Management, Wenzhou Medical University, Wenzhou 325035, PR China.
Email: [email protected]
Search for more papers by this authorFangfang Lu
Department of Preventive Medicine, School of Public Health and Management, Wenzhou Medical University, Zhejiang, China
Search for more papers by this authorQianqian Zhang
Department of Preventive Medicine, School of Public Health and Management, Wenzhou Medical University, Zhejiang, China
Department of Pharmacology, School of Pharmacy, Qilu Medical University, Shandong, China
Search for more papers by this authorMengyan Zhang
Department of Preventive Medicine, School of Public Health and Management, Wenzhou Medical University, Zhejiang, China
Search for more papers by this authorShuqiang Sun
Department of Preventive Medicine, School of Public Health and Management, Wenzhou Medical University, Zhejiang, China
Search for more papers by this authorXinjun Yang
Department of Preventive Medicine, School of Public Health and Management, Wenzhou Medical University, Zhejiang, China
Search for more papers by this authorCorresponding Author
Hongtao Yan
Department of Preventive Medicine, School of Public Health and Management, Wenzhou Medical University, Zhejiang, China
Correspondence
Hongtao Yan, Department of Preventive Medicine, School of Public Health and Management, Wenzhou Medical University, Wenzhou 325035, PR China.
Email: [email protected]
Search for more papers by this authorFunding information: National Natural Science Foundation of China, Grant/Award Number: 30972510; Natural Science Foundation of Zhejiang Province, Grant/Award Number: LY13H260003; Scientific and Technological Project of Wenzhou, Grant/Award Number: Y20160192
Abstract
There is in vivo and in vitro evidence that exposure to benzene or its metabolites could affect the mitochondrial function. However, the underlying molecular mechanism of mitochondrial damage remains to be elucidated. In this study, exposure of human promyelocytic leukemia cells (HL-60) to 1,4-benzoquinone (1,4-BQ; an active metabolite of benzene) increased the intracellular reactive oxygen species levels, decreased the mitochondrial membrane potential, adenosine triphosphate production and mitochondrial DNA (mtDNA) copy number, up-regulated the expression of mitochondrial fission proteins Drp1 and Fis1, and down-regulated the expression of mitochondrial fusion proteins Mfn2 and Opa1. Further study showed that 1,4-BQ mediated mitochondrial fission through activation of the AMP-activated protein kinase/mitochondrial fission factor/dynamin-related protein 1 pathway. Additionally, we also examined the role of exosomal secretion in mitochondrial damage under 1,4-BQ treatment. Results showed that 1,4-BQ increased the total protein level and mtDNA content in exosomes. Upon pre-treatment with the mitochondria-targeted antioxidant SS-31, there was attenuation of the mitochondrial damage induced by 1,4-BQ, accompanied by a change in the exosome release characteristics, while inhibition of exosomal secretion using GW4869 aggravated the 1,4-BQ-mediated mitochondrial fission. We concluded that exosomal secretion may serve as a self-protective mechanism of cells against 1,4-BQ-induced mitochondria damage and mitochondrial dynamics interference.
CONFLICT OF INTEREST
The authors declare that there are no conflicts of interest.
Open Research
DATA AVAILABILITY STATEMENT
The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.
Supporting Information
Filename | Description |
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jat4328-sup-0001-Figure_S1.tifTIFF image, 1.2 MB |
FIGURE S1 Identification of exosomes. (A) Representative image of exosomes observed using transmission electron microscopy (Scale bar: 100 nm). The arrows indicate exosomes, which are round or elliptical in shape. (B) The particle sizes of the exosomes were determined using nanoparticle tracking analysis (NTA). The peak particle size was 115.4 nm. (C) The surface markers of exosomes, CD9 and CD63, were detected using western blot. |
jat4328-sup-0002-Table_S1.docWord document, 30 KB |
Table S1 The primers used in this study. |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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