Mitochondrial bioenergetics and structural network organization
Mitochondrial bioenergetics and structural network organization
复制标题
线粒体生物能和结构网络组织
DOI：
10.1242/jcs.03381
复制
发表时间：
2007-03-01
影响因子：
4
通讯作者：
Rossignol, Rodrigue
中科院分区：
文献类型：
--
作者：
Benard, Giovanni;Bellance, Nadege;Rossignol, Rodrigue
线粒体形成了一个动态网络，目前还不清楚这些替代构型是如何与生物能量学特性相互作用的。将线粒体结构与其功能状态联系起来的代谢信号尚未完全确定。在这份报告中，我们分析了活着的人类细胞中线粒体形态和功能之间的双向关系。首先，我们通过针对Drp1的小干扰RNA(SiRNA)来确定线粒体分裂对能量产生的影响，这揭示了膜流动性在生物能量学控制中的重要性。其次，我们观察了鱼藤酮的效果，这是呼吸链复合体I的一种特异性抑制剂，一旦达到阈值，就会引起巨大的结构扰动。最后，我们观察了氧化磷酸化调节剂处理的人类细胞和两名线粒体疾病患者的成纤维细胞中线粒体网络结构的变化，并测量了呼吸频率、增量psi和活性氧物种(ROS)的产生。我们的数据表明线粒体网络组织和生物能量学之间的关系是双向的，我们为分析参与这种串扰的代谢信号提供了一个模型。
Mitochondria form a dynamic network, and it remains unclear how the alternate configurations interact with bioenergetics properties. The metabolic signals that link mitochondrial structure to its functional states have not been fully characterized. In this report, we analyze the bidirectional relationships between mitochondrial morphology and function in living human cells. First, we determined the effect of mitochondrial fission on energy production by using small interfering RNA ( siRNA) targeting DRP1, which revealed the importance of membrane fluidity on the control of bioenergetics. Second, we followed the effect of rotenone, a specific inhibitor of respiratory chain complex I, which causes large structural perturbations, once a threshold was reached. Last, we followed changes in the mitochondrial network configuration in human cells that had been treated with modulators of oxidative phosphorylation, and in fibroblasts from two patients with mitochondrial disease where the respiratory rate, Delta psi and the generation of reactive oxygen species (ROS) were measured. Our data demonstrate that the relationship between mitochondrial network organization and bioenergetics is bidirectional, and we provide a model for analyzing the metabolic signals involved in this crosstalk.