Abstract
Thyroid hormone (TH) regulates mitochondrial respiratory rate by activating coordinated transcription in the nucleus and mitochondria. Whereas TH activates transcription of mitochondrial genes directly, the activation of nuclear-encoded mitochondrial genes is probably executed by indirect unknown mechanisms. Nuclear respiratory factors (NRF)-1 and GA-binding protein (BP)/NRF-2 may function as transacting genes, but regulation of these genes by TH is not demonstrated. We show that TH administration to hypothyroid rats promptly increases GABP/NRF-2 alpha-subunit mRNA levels in the liver, without significant changes in beta, gamma subunits. In run-on and time-course experiments, the transcription rate and protein levels increased three-fold in response to TH, indicating GABP/NRF-2 transcriptional regulation. The results also support the notion that ATP synthase beta-subunit is regulated by TH through the indirect activation of GABP/NRF-2.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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ATP Synthetase Complexes / genetics
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ATP Synthetase Complexes / metabolism
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Animals
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism*
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Drug Administration Schedule
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GA-Binding Protein Transcription Factor
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Gene Expression Regulation / drug effects
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Gene Expression Regulation / physiology
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Hypothyroidism / drug therapy
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Hypothyroidism / metabolism
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Injections, Intraperitoneal
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Liver / drug effects*
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Liver / metabolism
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Male
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Mitochondrial Proteins*
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Nuclear Proteins / genetics
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Nuclear Proteins / metabolism
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Protein Subunits
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RNA, Messenger / metabolism
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Rats
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Rats, Wistar
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Time Factors
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Transcription Factors / genetics
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Transcription Factors / metabolism*
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Transcription, Genetic / drug effects*
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Triiodothyronine / administration & dosage*
Substances
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DNA-Binding Proteins
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GA-Binding Protein Transcription Factor
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Gabpa protein, rat
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Gabpb2 protein, rat
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Mitochondrial Proteins
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Nuclear Proteins
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Protein Subunits
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RNA, Messenger
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Tfam protein, rat
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Transcription Factors
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mitochondrial transcription factor A
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Triiodothyronine
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ATP Synthetase Complexes