The VDAC1 oligomerization regulated by ATP5B leads to the NLRP3 inflammasome activation in the liver cells under PFOS exposure

• Published in: Ecotoxicology and environmental safety 2024-08, Vol.281, p.116647, Article 116647
• Main Authors: Ma, Yu, Yang, Wei, Liang, Peiyao, Feng, Ruzhen, Qiu, Tianming, Zhang, Jingyuan, Sun, Xiance, Li, Qiujuan, Yang, Guang, Yao, Xiaofeng
• Format: Article
• Language: English
• Subjects: Alkanesulfonic Acids - toxicity; Animals; ATP5B; Cell Line; Environmental Pollutants - toxicity; Fluorocarbons - toxicity; Hepatocytes - drug effects; Hepatocytes - metabolism; Humans; Inflammasomes - drug effects; Inflammasomes - metabolism; Liver; Liver - drug effects; Liver - metabolism; Mice; Mice, Inbred C57BL; Mitochondria - drug effects; Mitochondria - metabolism; Mitochondrial Proton-Translocating ATPases - metabolism; NLR Family, Pyrin Domain-Containing 3 Protein - genetics; NLR Family, Pyrin Domain-Containing 3 Protein - metabolism; NLRP3 inflammasome; Perfluorooctane sulfonate; VDAC1 oligomers; Voltage-Dependent Anion Channel 1 - genetics; Voltage-Dependent Anion Channel 1 - metabolism
• ISSN: 0147-6513; 1090-2414; 1090-2414
• DOI: 10.1016/j.ecoenv.2024.116647

As a persistent organic pollutant, perfluorooctane sulfonate (PFOS) has a serious detrimental impact on human health. It has been suggested that PFOS is associated with liver inflammation. However, the underlying mechanisms are still unclear. Here, PFOS was found to elevate the oligomerization tendency of voltage-dependent anion channel 1 (VDAC1) in the mice liver and human normal liver cells L-02. Inhibition of VDAC1 oligomerization alleviated PFOS-induced nucleotide-binding domain and leucine-rich repeat protein-3 (NLRP3) inflammasome activation. Cytoplasmic membrane VDAC1 translocated to mitochondria was also observed in response to PFOS. Therefore, the oligomerization of VDAC1 occurred mainly in the mitochondria. VDAC1 was found to interact with the ATP synthase beta subunit (ATP5B) under PFOS treatment. Knockdown of ATP5B or immobilization of ATP5B to the cytoplasmic membrane alleviated the increased VDAC1 oligomerization and NLRP3 inflammasome activation. Therefore, our results suggested that PFOS induced NLRP3 inflammasome activation through VDAC1 oligomerization, a process dependent on ATP5B to transfer VDAC1 from the plasma membrane to the mitochondria. The findings offer novel perspectives on the activation of the NLRP3 inflammasome, the regulatory mode on VDAC1 oligomerization, and the mechanism of PFOS toxicity. [Display omitted] •PFOS induced the translocation and oligomerization of VDAC1.•PFOS-induced NLRP3 inflammasome activation was dependent on VDAC1 oligomerization.•Plasma membrane ATP5B transferred VDAC1 from the plasma membrane to mitochondria.•Plasma membrane ATP5B mediated the formation of VDAC1 oligomers.