Mitochondrial Actions of Thyroid Hormone

Abstract

The hypermetabolic effects of thyroid hormones (THs), the major endocrine regulators of metabolic rate, are widely recognized. Although, the cellular mechanisms underlying these effects have been extensively investigated, much has yet to be learned about how TH regulates diverse cellular functions. THs have a profound impact on mitochondria, the organelles responsible for the majority of cellular energy production, and several studies have been devoted to understand the respective importance of the nuclear and mitochondrial pathways for organelle activity. During the last decades, several new aspects of both THs (i.e., metabolism, transport, mechanisms of action, and the existence of metabolically active TH derivatives) and mitochondria (i.e., dynamics, respiratory chain organization in supercomplexes, and the discovery of uncoupling proteins other than uncoupling protein 1) have emerged, thus opening new perspectives to the investigation of the complex relationship between thyroid and the mitochondrial compartment. In this review, in the light of an historical background, we attempt to point out the present findings regarding thyroid physiology and the emerging recognition that mitochondrial dynamics as well as the arrangement of the electron transport chain in mitochondrial cristae contribute to the mitochondrial activity. We unravel the genomic and nongenomic mechanisms so far studied as well as the effects of THs on mitochondrial energetics and, principally, uncoupling of oxidative phosphorylation via various mechanisms involving uncoupling proteins. The emergence of new approaches to the question as to what extent and how the action of TH can affect mitochondria is highlighted. © 2016 American Physiological Society. Compr Physiol 6:1591-1607, 2016.

Testing for context-dependent effects of maternal thyroid hormones on offspring survival and physiology: an experimental approach manipulating temperature in a wild bird species

“…In contrast to our predictions, we did not observe clear context-dependent effects of THs on mtDNA copy number (hormone × heating, F1,155.8=0.55, p = 0.458, Fig 1d, Table S5), and also no apparent effect of prenatal TH elevation (F1,31.0=0.739, p=0.397, Table S5) or heating treatment (F1,41.5=0.003, p=0.958, Table S5) per se. While THs are known to affect mitochondrial biogenesis and function postnatally (25,26), only one previous study to our knowledge has investigated the effects of prenatal THs on mitochondrial parameters in a hypothyroid rat model. This study found no clear effects of prenatal THs on mitochondrial traits (28).…”

Thyroid hormone regulation of neural stem cell fate: From development to ageing

“…Such metabolic changes are crucial for NSC fate commitment and differentiation . THs are major modulators of cell metabolism, and TH‐induced mitochondrial responses are directly implicated in stem cell differentiation . Here, we will discuss how changes in cell metabolism influence NSC commitment and differentiation, and how TH signalling impacts cell metabolism during neurogenesis.…”

“…In addition, THs are major modulators of cell metabolism, by affecting genomic and non‐genomic pathways regulating mitochondrial activity . NSC determination and differentiation also implicate metabolic shifts.…”

Association of Diabetes Mellitus and Thyroid Disorders: A Metabolic Prospective

“…A large number of studies have reported the association between DM and TD [1][2][3][4][5], and evidenced a range of complex links between biochemical, genetic and hormonal malfunction sex planning their pathophysiological association [5][6][7]. In 1927, Coller and Huggins proved the association of hyperthyroidism and deterioration of diabetes and found that the subtotal thyroidectomy improves glucose tolerance in patients with hyperthyroidism with coexisting diabetes [8].…”