Blocking exosomal secretion aggravates 1, 4‐benzoquinone‐induced mitochondrial fission activated by the AMPK/MFF/Drp1 pathway in HL‐60 cells. Issue 10 (22nd May 2022)

• Record Type: Journal Article
• Authors: Lu, Fangfang; Zhang, Qianqian; Zhang, Mengyan; Sun, Shuqiang; Yang, Xinjun; Yan, Hongtao
• Is Part Of: Journal of applied toxicology. Volume 42:Issue 10(2022)
• Page Start: 1618
• Page End: 1627
• Publication Date: 2022-05-22
• Subjects: AMP‐activated protein kinase -- benzene -- exosome -- mitochondria -- mitochondrial dynamics; Toxicology -- Periodicals; Industrial toxicology -- Periodicals; Environmentally induced diseases -- Periodicals; Toxicology -- Periodicals; 615.9005
• DOI: 10.1002/jat.4328
• Languages: English
• ISSNs: 0260-437X

Abstract

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. Abstract : 1, 4‐benzoquinone (1, 4‐BQ; an active metabolite of benzene) led to mitochondrial dysfunction, mitochondrial fusion reduction and fission increase in HL‐60 cells. 1, 4‐BQ mediated mitochondrial fission through activation of the AMPK/MFF/Drp1 pathway. Inhibiting exosomal secretion by GW4869 aggravated 1, 4‐BQ‐induced mitochondrial fission. We concluded that exosomal secretion may be the self‐protective mechanism of cells against 1, 4‐BQ‐induced mitochondria damage and mitochondrial dynamics interference.