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

Abstract

Oxidative stress has many effects on biological cells, including the modulation of gene expression. Reactive oxygen species are known to up-regulate and down-regulate RNA expression in prokaryotic and eukaryotic cells. We have previously reported that a preferential and calcium-dependent down-regulation of mitochondrial RNAs occurs when HA-1 hamster fibroblasts are exposed to hydrogen peroxide. Here we extend these studies to determine whether this down-regulation is specific to mitochondria RNA or involves general polynucleotide degradation. Degradation and associated decreases in the levels of 16S mitochondrial rRNA following exposure of cells to 400 μM 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, and occurred at similar time points as for mitochondrial RNA degradation. As with mitochondrial RNA degradation, this mitochondrial genomic DNA degradation was dependent on calcium. These results indicate that there is a general, calcium-dependent degradation of mitochondrial polynucleotides following exposure of HA-1 fibroblasts to oxidative stress, and suggest that a dramatic shut-down in mitochondrial biosynthesis is an early-stage response to oxidative stress.