Abstract: Objective To study the effects of mitochondrial DNA(mtDNA)-depletion and mitochondrial functional deficiency on the expression of nuclear DNA.Methods Using human whole-genome chip,the expression profiles of nuclear DNA in mtDNA-depleted HepG2 cells and mitochondrial function deficient HepG2 cells were analyzed.Results Among 41 000 genes,there were 5 489 genes differentially expressed in mtDNA-depleted HepG2 cells compared with normal HepG2 cells(the fold change≧2.0),with 3 350 up-regulated and 2 139 down-regulated.In mitochondrial function de ficient HepG2 cells, there were 3334 genes differentially expressed, with 1457 up regulated and 1877 down regulated.The effects of mtDNA depletion and mitochondrial function deficiency on cell signaling pathways were significantly different and imposed different effects on different signaling pathways.Conclusion Both mtDNA depletion and mito chondrial function de ficiency induce significant different expression of nuclear DNA.The effect of mtDNA depletion ismore serious as compared with that of mitochondrial function deficiency.The mechanism may underlie the different effects on different signaling pathways.