Objective：The current study aims to investigate the molecular mechanism of mitochondrial unfolded protein reaction (mtUPR)induced by down - regulation of dynamin related protein 1(Drp1)expression in mouse embryonic fibroblast(MEF)cells. Methods：The expression levels of CCAAT/enhancer-binding protein homologous protein(CHOP)，ATP binding cassette subfamily B member 10(ABCB10)，Lon peptidase 1(LONP1)and heat shock protein 60(Hsp60)were detected by Western blot in Drp1 KO/KD cells，MEF cells treated with Drp1 inhibitors Mdivi1 or P110 and control cells after administration of 3-nitropropionic acid(3-NP)at different concentrations(0，2.5，5.0，10.0 mol/L). RT-qPCR was used to detect ABCB10 mRNA levels in Drp1 KD or Mdivi-1 treated MEF cells. After Drp1/ABCB10 double knocking down，the expression levels of CHOP protein was detected by Western blot，lactate dehydrogenase(LDH)release assay kit was used to detect the content of LDH in culture medium，and the levels of mitochondrial reactive oxygen and membrane potential were detected by flow cytometry. Results：The expression levels of CHOP were upregulated in Drp1 KO/KD cells or MEF cells treated with Drp1 inhibitors Mdivi-1 or P110. The expression levels of ABCB10 and mtUPR related proteins LONP1 and Hsp60 were upregulated in Drp1 KO/KD cells or MEF cells treated with Drp1 inhibitors Mdivi - 1 or P110. Compared with control groups，the mRNA levels of ABCB10 were upregulated in Drp1 KD or Mdivi -1 treated MEF cells. After both Drp1 and ABCB10 knocking down，the expression levels CHOP was down - regulated，LDH content was decreased，mitochondrial reactive oxygen level was decreased，and mitochondrial membrane potential level was increased. Conclusion：Deficiency of Drp1 activates the mtUPR through ABCB10，which causes the upregulation of the mtUPR proteins CHOP，LONP1 and Hsp60.