Physiological diversity of mitochondrial oxidative phosphorylation
Physiological diversity of mitochondrial oxidative phosphorylation
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DOI：
10.1152/ajpcell.00195.2006
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发表时间：
2006-12-01
影响因子：
5.5
通讯作者：
Rossignol, R.
中科院分区：
文献类型：
--
作者：
Benard, G.;Faustin, B.;Rossignol, R.
为了研究线粒体氧化磷酸化调控的生理多样性，我们测定了肌肉、心脏、肝脏、肾脏和脑中呼吸链的组成和功能特征。首先，我们通过不同组织切片的电子显微照片观察到线粒体内容和基础结构的重要变化。蛋白质印迹分析显示呼吸链酶含量在不同组织间差异较大，与线粒体转录因子A的表达水平和柠檬酸合成酶的活性有很好的相关性。在分离的线粒体上，我们观察到呼吸链复合体之间的摩尔比是保守的，辅酶Q和细胞色素c的化学计量比是可变的，不同组织中的复合体II：辅酶Q：复合体III：细胞色素C：复合体IV的典型值为[1-1.5]：[30-135]：[3]：[9-35]：[6.5-7.5]。功能分析显示呼吸链复合体的最大速度有显著差异，心脏的最大速度值较高。然而，催化常数的计算表明，大脑中含有更活跃的酶复合体。因此，我们的研究表明，在组织中，氧化磷酸化能力是高度可变和多样化的，这取决于1)线粒体含量，2)呼吸链复合体的数量，以及3)其内在活性的不同组合。在所有组织中，与状态3呼吸所需的相比，存在大量过剩的酶能力和中间底物浓度。总而言之，我们将数据提交给主成分分析，发现了三组组织：肌肉和心脏、脑和肝和肾。
To investigate the physiological diversity in the regulation and control of mitochondrial oxidative phosphorylation, we determined the composition and functional features of the respiratory chain in muscle, heart, liver, kidney, and brain. First, we observed important variations in mitochondrial content and infrastructure via electron micrographs of the different tissue sections. Analyses of respiratory chain enzyme content by Western blot also showed large differences between tissues, in good correlation with the expression level of mitochondrial transcription factor A and the activity of citrate synthase. On the isolated mitochondria, we observed a conserved molar ratio between the respiratory chain complexes and a variable stoichiometry for coenzyme Q and cytochrome c, with typical values of [1-1.5]:[30-135]:[3]:[9-35]:[6.5-7.5] for complex II: coenzyme Q: complex III: cytochrome c: complex IV in the different tissues. The functional analysis revealed important differences in maximal velocities of respiratory chain complexes, with higher values in heart. However, calculation of the catalytic constants showed that brain contained the more active enzyme complexes. Hence, our study demonstrates that, in tissues, oxidative phosphorylation capacity is highly variable and diverse, as determined by different combinations of 1) the mitochondrial content, 2) the amount of respiratory chain complexes, and 3) their intrinsic activity. In all tissues, there was a large excess of enzyme capacity and intermediate substrate concentration, compared with what is required for state 3 respiration. To conclude, we submitted our data to a principal component analysis that revealed three groups of tissues: muscle and heart, brain, and liver and kidney.