Oxidative stress causes a general, calcium-dependent degradation of mitochondrial polynucleotides

Oxidative stress has many effects on biological cells, including the modula tion of gene expression. Reactive oxygen species are known to up-regulate a nd down-regulate RNA expression in prokaryotic and eukaryotic cells. We hav e previously reported that a preferential and calcium-dependent down-regula tion of mitochondrial RNAs occurs when HA-I hamster fibroblasts are exposed to hydrogen peroxide. Here we extend these studies to determine whether th is down-regulation is specific to mitochondria RNA or involves general poly nucleotide degradation. Degradation and associated decreases in the levels of 16S mitochondrial rRNA following exposure of cells to 400 mu M hydrogen peroxide were found to be dependent on calcium at 2 and 5 h. Degradation of mitochondrial genomic DNA was also observed following peroxide exposure, a nd occurred at similar time points as for mitochondrial RNA degradation. As with mitochondrial RNA degradation, this mitochondrial genomic DNA degrada tion was dependent on calcium. These results indicate that-there is a gener al, calcium-dependent degradation of mitochondrial polynucleotides followin g exposure of HA-1 fibroblasts to oxidative stress, and suggest that a dram atic shut-down in mitochondrial biosynthesis is an early-stage response to oxidative stress. (C) 1998 Elsevier Science Inc.