Effect of thyroid hormone on mtHsp70 expression, mitochondrial import and processing in cardiac muscle.
Mitochondrial heat shock protein 70 (mtHsp70), an important mitochondrial chaperone, 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 them with 3,3', 5-triiodo-l-thyronine (T(3)) for 5 days, or by treating them with vehicle. In Series II, animals were given 6-n-propyl-2-thiouracil in their drinking water (0.05% w/v) for a period of 32-42 days to make them hypothyroid. During the last 5 days of treatment these animals received injections 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 transcriptional regulation. However, evidence of tissue-specific post-transcriptional regulation was also apparent. In isolated heart mitochondria, T(3) treatment 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 hypothyroid animals, and it could not be attributed to an altered rate of intramitochondrial mtHsp70 degradation. The rate of processing of mtHsp70 to its mature form, reflecting mitochondrial processing peptidase activity, was unaffected by T(3), but was more rapid than mtHsp70 import. These data indicate a novel mechanism by which T(3) modifies the mitochondrial phenotype via the adaptations in the protein import pathway.
Schneider
J J
JJ
Departments of Kinesiology and Health Science and Biology, York University, Toronto, Ontario, Canada, M3J 1P3.
Hood
D A
DA
D000818:Animals; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000502:physiology*; D006980:Hyperthyroidism / Q000503:physiopathology; D007037:Hypothyroidism / Q000139:chemically induced / Q000503:physiopathology; D008297:Male; D008929:Mitochondria, Heart / Q000502:physiology*; D011441:Propylthiouracil / Q000009:adverse effects; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014158:Transcription, Genetic; D014284:Triiodothyronine / Q000502:physiology*
D018840:HSP70 Heat-Shock Proteins; D012333:RNA, Messenger; D014284:Triiodothyronine; D011441:Propylthiouracil