Volume 42, Issue 10 p. 1618-1627
RESEARCH ARTICLE

Blocking exosomal secretion aggravates 1,4-benzoquinone-induced mitochondrial fission activated by the AMPK/MFF/Drp1 pathway in HL-60 cells

Fangfang Lu

Fangfang Lu

Department of Preventive Medicine, School of Public Health and Management, Wenzhou Medical University, Zhejiang, China

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Qianqian Zhang

Qianqian 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

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Mengyan Zhang

Mengyan Zhang

Department of Preventive Medicine, School of Public Health and Management, Wenzhou Medical University, Zhejiang, China

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Shuqiang Sun

Shuqiang Sun

Department of Preventive Medicine, School of Public Health and Management, Wenzhou Medical University, Zhejiang, China

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Xinjun Yang

Xinjun Yang

Department of Preventive Medicine, School of Public Health and Management, Wenzhou Medical University, Zhejiang, China

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Hongtao Yan

Corresponding 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]

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First published: 05 April 2022
Citations: 2

Funding 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.

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.