THE MITOCHONDRION AS A PRIMARY SITE OF ACTION OF GLUCOCORTICOIDS - THE INTERACTION OF THE GLUCOCORTICOID RECEPTOR WITH MITOCHONDRIAL-DNA SEQUENCES SHOWING PARTIAL SIMILARITY TO THE NUCLEAR GLUCOCORTICOID-RESPONSIVE ELEMENTS

Six mitochondrial genome sequences, showing strong similarity to the g lucocorticoid responsive element consensus sequence (GRE), four locali zed within the cytochrome c oxidase (COX) subunit I and III genes (GRE s I-IV) and two within the D-loop region (GREs a and b) have been exam ined as binding sites of glucocorticoid receptor (GR) from rat liver c ytosol. Purified GR from rat liver cytosol binds with high specificity to all potential mitochondrial GREs, as shown by filter retention and gel shift assays. Specific binding of protein(s), present in a mitoch ondrial extract from dexamethasone-induced mice, to all six putative m itochondrial GREs was also documented by the same methodology. Both pu rified GR and protein(s) from mitochondrial extract give the same band in the gel retardation assay. Using monospecific anti-glucocorticoid receptor polyclonal antibody (EP), a supershift of the gel retarded pr otein-DNA band was obtained. These results demonstrate that the mitoch ondrial genome sequences examined have characteristics of GREs, since they show the capacity to specifically bind the respective receptor pr otein. These findings support the hypothesis that the mitochondrial ge nome is a primary site of action of steroid and thyroid hormones (Seke ris C.E.: The mitochondrial genome: a possible primary site of action of steroid hormones, In vivo 4 (1990) 317-320).