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Chronic fluorosis alters the dynamic balance between mitochondrial fusion and division. The present study investigated the effect of mitochondrial fusion function on apoptosis before or after downregulation of the expression of fission 1 (Fis1) protein in SH-SY5Y cells exposed to excessive fluoride. The expressions of Fis1 and mitofusin 1 (Mfn1) at mRNA and protein levels and the mitochondrial membrane potential level (MMPL) were detected by real-time PCR, Western blot and fluorescence microscopy, respectively. The degree of apoptosis was determined by proliferation toxicity assay. The results showed the upregulation of Fis1 protein and the downregulation of Mfn1 protein, and the decrease in MMPL content due to apoptosis in SH-SY5Y cells exposed to fluoride. Interestingly, these effects were attenuated after the expression of Fis1 protein was inhibited. Taken together, these findings suggested that the toxic effect of fluoride on the target cells might be involved in the Fis1 and Mfn1 protein-related disorder, which eventually led to mitochondrial apoptosis in neurons. [ABSTRACT FROM AUTHOR]