Glucocorticoid and thyroid hormone receptors in mitochondria of animal cells

Abstract

This article concerns the localization of glucocorticoid and thyroid hormone receptors in mitochondria of animal cells. The receptors are discussed in terms of their potential role in the regulation of mitochondrial transcription and energy production by the oxidative phosphorylation pathway, realized both by nuclear-encoded and mitochondrially encoded enzymes. A brief survey of the role of glucocorticoid and thyroid hormones on energy metabolism is presented, followed by a description of the molecular mode of action of these hormones and of the central role of the receptors in regulation of transcription. Subsequently, the structure and characteristics of glucocorticoid and thyroid hormone receptors are described, followed by a section on the effects of glucocorticoid and thyroid hormones on the transcription of mitochondrial and nuclear genes encoding subunits of OXPHOS and by an introduction to the mitochondrial genome and its transcription. A comprehensive description of the data demonstrates the localization of glucocorticoid and thyroid hormone receptors in mitochondria as well as the detection of potential hormone response elements that bind to these receptors. This leads to the conclusion that the receptors potentially play a role in the regulation of transcription of mitochondrial genes. The in organello mitochondrial system, which is capable of sustaining transcription in the absence of nuclear participation, is presented, responding to T3 with increased transcription rates, and the central role of a thyroid receptor isoform in the transcription effect is emphasized. Lastly, possible ways of coordinating nuclear and mitochondrial gene transcription in response to glucocorticoid and thyroid hormones are discussed, the hormones acting directly on the genes of the two compartments by way of common hormone response elements and indirectly on mitochondrial genes by stimulation of nuclear-encoded transcription factors.