Thyroid hormone effects on mitochondrial energetics.
Thyroid hormones are the major endocrine regulators of metabolic rate, and their hypermetabolic effects are widely recognized. The cellular mechanisms underlying these metabolic effects have been the subject of much research. Thyroid hormone status has a profound impact on mitochondria, the organelles responsible for the majority of cellular adenosine triphosphate (ATP) production. However, mechanisms are not well understood. We review the effects of thyroid hormones on mitochondrial energetics and principally oxidative phosphorylation. Genomic and nongenomic mechanisms have been studied. Through the former, thyroid hormones stimulate mitochondriogenesis and thereby augment cellular oxidative capacity. Thyroid hormones induce substantial modifications in mitochondrial inner membrane protein and lipid compositions. Results are consistent with the idea that thyroid hormones activate the uncoupling of oxidative phosphorylation through various mechanisms involving inner membrane proteins and lipids. Increased uncoupling appears to be responsible for some of the hypermetabolic effects of thyroid hormones. ATP synthesis and turnover reactions are also affected. There appear to be complex relationships between mitochondrial proton leak mechanisms, reactive oxygen species production, and thyroid status. As the majority of studies have focused on the effects of thyroid status on rat liver preparations, there is still a need to address fundamental questions regarding thyroid hormone effects in other tissues and species.
Harper
Mary-Ellen
ME
Department of Biochemistry, Microbiology, and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada. maryellen.harper@uottawa.ca
Seifert
Erin L
EL
D000255:Adenosine Triphosphate; D000818:Animals; D004734:Energy Metabolism; D006801:Humans; D008563:Membrane Lipids / Q000378:metabolism; D051379:Mice; D008928:Mitochondria / Q000378:metabolism*; D051336:Mitochondrial Membranes / Q000378:metabolism; D010085:Oxidative Phosphorylation; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D013963:Thyroid Hormones / Q000378:metabolism*
D008563:Membrane Lipids; D017382:Reactive Oxygen Species; D013963:Thyroid Hormones; D000255:Adenosine Triphosphate