GP Livanos and M Simou Laboratories, Evangelismos Hospital, Department of Critical Care and Pulmonary Services, University of Athens Medical School, Athens, Greece.
PLoS One. 2012;7(6):e39183. doi: 10.1371/journal.pone.0039183. Epub 2012 Jun 27.
Mitochondrial glucocorticoid (mtGR) and estrogen (mtER) receptors participate in the coordination of the cell's energy requirement and in the mitochondrial oxidative phosphorylation enzyme (OXPHOS) biosynthesis, affecting reactive oxygen species (ROS) generation and induction of apoptosis. Although activation of mtGR and mtER is known to trigger anti-inflammatory signals, little information exists on the presence of these receptors in lung tissue and their role in respiratory physiology and disease. Using a mouse model of allergic airway inflammation disease and applying confocal microscopy, subcellular fractionation, and Western blot analysis we showed mitochondrial localization of GRα and ERβ in lung tissue. Allergic airway inflammation caused reduction in mtGRα, mtERβ, and OXPHOS enzyme biosynthesis in lung cells mitochondria and particularly in bronchial epithelial cells mitochondria, which was accompanied by decrease in lung mitochondrial mass and induction of apoptosis. Confirmation and validation of the reduction of the mitochondrial receptors in lung epithelial cells in human asthma was achieved by analyzing autopsies from fatal asthma cases. The presence of the mitochondrial GRα and ERβ in lung tissue cells and especially their reduction in bronchial epithelial cells during allergic airway inflammation suggests a crucial role of these receptors in the regulation of mitochondrial function in asthma, implicating their involvement in the pathophysiology of the disease.
线粒体糖皮质激素（mtGR）和雌激素（mtER）受体参与细胞能量需求的协调以及线粒体氧化磷酸化酶（OXPHOS）的生物合成，影响活性氧（ROS）的产生和细胞凋亡的诱导。虽然已知 mtGR 和 mtER 的激活会引发抗炎信号，但关于这些受体在肺组织中的存在及其在呼吸生理和疾病中的作用的信息很少。本研究使用过敏性气道炎症疾病的小鼠模型，并应用共聚焦显微镜、亚细胞分级分离和 Western blot 分析，我们在肺组织中显示了 GRα 和 ERβ 的线粒体定位。过敏性气道炎症导致肺细胞线粒体，特别是支气管上皮细胞线粒体中 mtGRα、mtERβ 和 OXPHOS 酶生物合成减少，同时伴有肺线粒体质量减少和细胞凋亡诱导。通过分析致命性哮喘病例的尸检，证实并验证了肺上皮细胞中线粒体受体的减少。线粒体 GRα 和 ERβ 存在于肺组织细胞中，特别是在过敏性气道炎症期间支气管上皮细胞中的减少，表明这些受体在哮喘中线粒体功能的调节中起着至关重要的作用，提示它们参与了疾病的病理生理学。
