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Am J Physiol Endocrinol Metab. 2004 Jun;286(6):E968-74. Epub 2004 Feb 17.

Tissue-specific regulation of cytochrome c oxidase subunit expression by thyroid hormone.

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School of Kinesiology and Health Science, York University, Toronto, Ontario, Canada.


The influence of thyroid hormone (T(3)) on respiration is partly mediated via its effect on the cytochrome c oxidase (COX) enzyme, a multi-subunit complex within the mitochondrial respiratory chain. We compared the expression of COX subunits I, III, Vb, and VIc and thyroid receptors (TR)alpha1 and TRbeta1 with functional changes in COX activity in tissues that possess high oxidative capacities. In response to 5 days of T(3) treatment, TRbeta1 increased 1.6-fold in liver, whereas TRalpha1 remained unchanged. T(3) also induced concomitant increases in the protein and mRNA expression of nuclear-encoded subunit COX Vb in liver, matched by a 1.3-fold increase in binding to a putative thyroid response element (TRE) within the COX Vb promoter in liver, suggesting transcriptional regulation. In contrast, T(3) had no effect on COX Vb expression in heart. T(3) produced a significant increase in COX III mRNA in liver but decreased COX III mRNA in heart. These changes were matched by parallel alterations in mitochondrial transcription factor A expression in both tissues. In contrast, COX I protein increased in both liver and heart 1.7- and 1.5-fold (P < 0.05), respectively. These changes in COX I closely paralleled the T(3)-induced increases in COX activity observed in both of these tissues. In liver, T(3) induced a coordinated increase in the expression of the nuclear (COX Vb) and mitochondrial (COX I) genomes at the protein level. However, in heart, the main effect of T(3) was restricted to the expression of mitochondrial DNA subunits. Thus our data suggest that T(3) regulates the expression of COX subunits by both transcriptional and posttranscriptional mechanisms. The nature of this regulation differs between tissues possessing a high mitochondrial content, like liver and heart.

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