Effect of thyroid hormone on mtHsp70 expression, mitochondrial import and processing in cardiac muscle

Mitochondrial heat shock protein 70 (mtHsp70), an important mitochondrial c haperone, is increased in cardiac muscle mitochondria of hyperthyroid rats. To determine the mechanism(s) underlying this increase, we used variations in thyroid status. In Series I, rats were made hyperthyroid by injecting t hem with 3,3',5-triiodo-L-thyronine (T-3) for 5 days, or by treating them w ith vehicle. In Series II, animals were given 6-n-propyl-2-thiouracil in th eir drinking water (0.05% w/v) for a period of 32-42 days to make them hypo thyroid. During the last 5 days of treatment these animals received injecti ons of either T-3, or vehicle. T-3 treatment resulted in parallel increases in mtHsp70 protein and mRNA levels in a variety of tissues, suggesting tra nscriptional regulation. However, evidence of tissue-specific post-transcri ptional regulation was also apparent. In isolated heart mitochondria, T-3 t reatment resulted in a 1.8-fold increase in mtHsp70. This was due to the 1. 6-fold greater import of mtHsp70 into mitochondria in T-3, compared with hy pothyroid animals, and it could not be attributed to an altered rate of int ramitochondrial mtHsp70 degradation. The rate of processing of mtHsp70 to i ts mature form, reflecting mitochondrial processing peptidase activity, was unaffected by T-3, but was more rapid than mtHsp70 import. These data indi cate a novel mechanism by which T-3 modifies the mitochondrial phenotype vi a the adaptations in the protein import pathway.