Estrogenic control of mitochondrial function
Estrogenic control of mitochondrial function
复制标题
DOI：
10.1016/j.redox.2020.101435
复制
发表时间：
2020-04-01
期刊：
影响因子：
11.4
通讯作者：
Klinge, Carolyn M.
中科院分区：
文献类型：
--
作者：
Klinge, Carolyn M.
人类疾病的性别差异部分是由调节线粒体代谢的内源性性类固醇激素水平引起的。这篇综述更新了2017年发表的一篇关于雌激素如何调节代谢和线粒体功能的综述。雌激素由卵巢和肾上腺产生，少量由脂肪、乳腺基质和脑组织产生。在细胞水平上，雌激素调节包括生殖和行为在内的多种细胞功能的机制是通过与雌激素受体α、β （ER α和ER β）和g蛋白偶联ER （GPER1）结合。内质网α和内质网β是结合基因组和线粒体DNA调控基因转录的转录因子。一小部分内质网α和内质网β与质膜相关信号蛋白相互作用，激活细胞内信号级联，最终改变转录反应，包括线粒体形态和功能。尽管雌激素直接或间接调节线粒体功能的机制和目标尚未完全阐明，但很明显雌二醇通过核和线粒体介导的事件调节线粒体代谢和形态，包括刺激核呼吸因子-1 （NRF-1）转录，这将在这里进行综述。NRF-1是一种转录因子，可与辅助激活因子相互作用，包括过氧化物酶体增殖体激活受体γ，辅助激活因子1 α (PGC-1 α)，以调节核编码的线粒体基因。NRF-1的一个靶标是TFAM，它结合mtDNA来调节其转录。核编码的miRNA和lncRNA调控mtdna编码的转录本和核编码的转录本调控线粒体功能，从而起到顺行信号的作用。其他雌激素调节的线粒体活动包括生物能量学，氧气消耗率（OCR）和细胞外酸化（ECAR）。
Sex-based differences in human disease are caused in part by the levels of endogenous sex steroid hormones which regulate mitochondrial metabolism. This review updates a previous review on how estrogens regulate metabolism and mitochondrial function that was published in 2017. Estrogens are produced by ovaries and adrenals, and in lesser amounts by adipose, breast stromal, and brain tissues. At the cellular level, the mechanisms by which estrogens regulate diverse cellular functions including reproduction and behavior is by binding to estrogen receptors alpha, beta (ER alpha and ER beta) and G-protein coupled ER (GPER1). ER alpha and ER beta are transcription factors that bind genomic and mitochondrial DNA to regulate gene transcription. A small proportion of ER alpha and ER beta interact with plasma membrane-associated signaling proteins to activate intracellular signaling cascades that ultimately alter transcriptional responses, including mitochondrial morphology and function. Although the mechanisms and targets by which estrogens act directly and indirectly to regulate mitochondrial function are not fully elucidated, it is clear that estradiol regulates mitochondrial metabolism and morphology via nuclear and mitochondrial-mediated events, including stimulation of nuclear respiratory factor-1 (NRF-1) transcription that will be reviewed here. NRF-1 is a transcription factor that interacts with coactivators including peroxisome proliferator-activated receptor gamma, coactivator 1 alpha (PGC-1 alpha) to regulate nuclear-encoded mitochondrial genes. One NRF-1 target is TFAM that binds mtDNA to regulate its transcription. Nuclear-encoded miRNA and lncRNA regulate mtDNA-encoded and nuclear-encoded transcripts that regulate mitochondrial function, thus acting as anterograde signals. Other estrogen-regulated mitochondrial activities including bioenergetics, oxygen consumption rate (OCR), and extracellular acidification (ECAR), are reviewed.