Grupo Multidisciplinar de Oncología Traslacional, Institut d'Investigació en Ciències de la Salut, Universitat de les Illes Balears, Crta. Valldemossa Km 7.5, 07122 Palma de Mallorca, Illes Balears, Spain.
Int J Biochem Cell Biol. 2013 Jul;45(7):1509-15. doi: 10.1016/j.biocel.2013.04.007. Epub 2013 Apr 22.
Mitochondrial biogenesis and function are under the control of 17β-estradiol, which acts through two distinct estrogen receptors (alpha or beta), and the estrogen receptors ratio can determine the final effect of 17β-estradiol on mitochondria. Our aim was to study the effects of 17β-estradiol on mitochondrial biogenesis, dynamics and function in breast cancer cell lines with different estrogen receptors ratios. Mitochondrial biogenesis was increased in MDA-MB-231 (with only estrogen receptor beta expression), T47D (normal estrogen receptors ratio) and MCF-7 (highest estrogen receptors ratio) breast cancer cell lines, in response to different mitochondrial and cellular status. In fact, mitochondria of the MDA-MB-231 and T47D cell lines maintained their functionality, although, the MCF-7 cell line did suffer an important decrease in mitochondrial function. Thus, mitochondrial biogenesis increased in MCF-7 with the aim of mitigating these defective mitochondria. In normal conditions, mitophagic processes remove defective mitochondria to refresh the mitochondrial pool. Mitochondrial dynamics were also under control by 17β-estradiol, and showed modifications in the fusion/fission processes and the modulation of mitochondrial removal. In fact, cells with only estrogen receptor beta or with a low estrogen receptors ratio, such as MDA-MB-231 and T47D, showed an increase in fusion processes. However, the MCF-7 cell line, with more estrogen receptor alpha, also showed an increase in fusion processes, even though the fission processes were diminished and led to an accumulation of unfunctional mitochondria. Finally, the importance of estrogen receptor beta in mitochondrial biogenesis, function, as well as in mitochondrial dynamics was examined. Using the T47D-estrogen receptor beta tetracycline-inducible cell line, the results confirmed that when the overexpression of estrogen receptor beta was inhibited, there was an increase in mitochondrial biogenesis, although these mitochondria were less functional, and with fewer fission events, although there was an increase in fusion processes.
线粒体生物发生和功能受 17β-雌二醇的控制，17β-雌二醇通过两种不同的雌激素受体（α或β）发挥作用，而雌激素受体的比例可以决定 17β-雌二醇对线粒体的最终影响。我们的目的是研究不同雌激素受体比例的乳腺癌细胞系中 17β-雌二醇对线粒体生物发生、动力学和功能的影响。
在 MDA-MB-231（仅表达雌激素受体β）、T47D（正常雌激素受体比例）和 MCF-7（雌激素受体比例最高）乳腺癌细胞系中，线粒体生物发生增加，以响应不同的线粒体和细胞状态。事实上，尽管 MDA-MB-231 和 T47D 细胞系的线粒体保持其功能，但 MCF-7 细胞系的线粒体功能确实严重下降。因此，MCF-7 中线粒体生物发生的增加旨在减轻这些有缺陷的线粒体。在正常情况下，噬线粒体过程会清除有缺陷的线粒体，以更新线粒体池。
17β-雌二醇也控制着线粒体动力学，并在融合/裂变过程和线粒体去除的调节方面进行了修饰。事实上，只有雌激素受体β或雌激素受体比例低的细胞，如 MDA-MB-231 和 T47D，显示融合过程增加。然而，MCF-7 细胞系，具有更多的雌激素受体α，也显示出融合过程的增加，即使裂变过程减少，并导致无功能线粒体的积累。
最后，研究了雌激素受体β在线粒体生物发生、功能以及线粒体动力学中的重要性。使用 T47D-雌激素受体β四环素诱导细胞系，结果证实，当过度表达的雌激素受体β被抑制时，线粒体生物发生增加，尽管这些线粒体的功能较低，裂变事件较少，但融合过程增加。
