Thyroid hormone and gene expression in the regulation of mitochondrial respiratory function

Thyroid hormone has a profound effect on cellular respiration. Abnormally high levels of this hormone accelerate respiration in conjunction with a general increase in metabolism while pathologically low amounts cause low levels of respiration with a general slowing of metabolic activity. The affect on respiration is primarily the result of changes in the expression of respiratory genes and modulation of inner membrane structure. This review focuses on the regulation of respiratory gene expression by thyroid hormone. Respiratory genes are encoded in both the nucleus and the mitochondrion, the products of which are required in stoichiometric amounts for proper assembly of the respiratory chain. Thyroid hormone influences the expression of a number of nuclear encoded respiratory genes at the level of mRNA and enhances expression of mitochondrially encoded respiratory genes. Therefore, thyroid hormone appears to affect gene regulation in two different cell compartments. The current evidence for a direct thyroid hormone/thyroid receptor regulation of these respiratory genes and possible indirect pathway(s) mediating the thyroid effect is discussed.