Thyroid hormone effects on mitochondrial energetics
Thyroid hormone effects on mitochondrial energetics
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DOI：
10.1089/thy.2007.0250
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发表时间：
2008-02-01
期刊：
影响因子：
6.6
通讯作者：
Seifert, Erin L.
中科院分区：
文献类型：
--
作者：
Harper, Mary-Ellen;Seifert, Erin L.
甲状腺激素是代谢率的主要内分泌调节因子，其高代谢作用已被广泛认识。这些代谢效应的细胞机制一直是许多研究的主题。甲状腺激素状态对线粒体有深远的影响，线粒体是负责大部分细胞三磷酸腺苷（ATP）产生的细胞器。然而，机制并不十分清楚。我们回顾甲状腺激素对线粒体能量学的影响，主要是氧化磷酸化。基因组和非基因组机制已被研究。通过前者，甲状腺激素刺激促甲状腺激素生成，从而增加细胞的氧化能力。甲状腺激素诱导线粒体内膜蛋白和脂质组成的实质性改变。结果与甲状腺激素通过涉及内膜蛋白和脂质的各种机制激活氧化磷酸化解偶联的想法一致。增加解偶联似乎是负责一些甲状腺激素的高代谢作用。ATP合成和周转反应也受到影响。线粒体质子泄漏机制、活性氧产生和甲状腺状态之间似乎存在复杂的关系。由于大多数研究都集中在甲状腺状态对大鼠肝脏制剂的影响上，因此仍然需要解决有关甲状腺激素对其他组织和物种影响的基本问题。
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.