Arvier Matthieu, Lagoutte Laëtitia, Johnson Gyasi, Dumas Jean-François, Sion Benoit, Grizard Genevieve, Malthièry Yves, Simard Gilles, Ritz Patrick
Institut National de la Santé et de la Recherche Médicale, Laboratoire de Biochimie et de Biologie Moléculaire, Centre Hospitalier Universitaire, Angers, France.
Am J Physiol Endocrinol Metab. 2007 Nov;293(5):E1320-4. doi: 10.1152/ajpendo.00138.2007. Epub 2007 Aug 14.
The composition of the mitochondrial inner membrane and uncoupling protein [such as adenine nucleotide translocator (ANT)] contents are the main factors involved in the energy-wasting proton leak. This leak is increased by glucocorticoid treatment under nonphosphorylating conditions. The aim of this study was to investigate mechanisms involved in glucocorticoid-induced proton leak and to evaluate the consequences in more physiological conditions (between states 4 and 3). Isolated liver mitochondria, obtained from dexamethasone-treated rats (1.5 mg.kg(-1).day(-1)), were studied by polarography, Western blotting, and high-performance thin-layer chromatography. We confirmed that dexamethasone treatment in rats induces a proton leak in state 4 that is associated with an increased ANT content, although without any change in membrane surface or lipid composition. Between states 4 and 3, dexamethasone stimulates ATP synthesis by increasing both the mitochondrial ANT and F1-F0 ATP synthase content. In conclusion, dexamethasone increases mitochondrial capacity to generate ATP by modifying ANT and ATP synthase. The side effect is an increased leak in nonphosphorylating conditions.
线粒体内膜的组成以及解偶联蛋白[如腺嘌呤核苷酸转位酶（ANT）]的含量是导致能量消耗性质子泄漏的主要因素。在非磷酸化条件下，糖皮质激素处理会增加这种泄漏。本研究的目的是探究糖皮质激素诱导质子泄漏的机制，并评估在更接近生理状态（状态4和状态3之间）下的后果。通过极谱法、蛋白质免疫印迹法和高效薄层色谱法，对从地塞米松处理的大鼠（1.5 mg·kg⁻¹·天⁻¹）分离得到的肝线粒体进行了研究。我们证实，大鼠经地塞米松处理后，在状态4时会诱导质子泄漏，这与ANT含量增加有关，尽管膜表面积或脂质组成没有任何变化。在状态4和状态3之间，地塞米松通过增加线粒体ANT和F1-F0 ATP合酶的含量来刺激ATP合成。总之，地塞米松通过改变ANT和ATP合酶来增加线粒体产生ATP的能力。副作用是在非磷酸化条件下泄漏增加。
