PGC-1-related coactivator modulates mitochondrial-nuclear crosstalk through endogenous nitric oxide in a cellular model of oncocytic thyroid tumours.
PGC-1-related coactivator modulates mitochondrial-nuclear crosstalk through endogenous nitric oxide in a cellular model of oncocytic thyroid tumours.
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DOI：
10.1371/journal.pone.0007964
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发表时间：
2009-11-23
期刊：
影响因子：
3.7
通讯作者：
Savagner F
中科院分区：
文献类型：
--
作者：
Raharijaona M;Le Pennec S;Poirier J;Mirebeau-Prunier D;Rouxel C;Jacques C;Fontaine JF;Malthiery Y;Houlgatte R;Savagner F
PGC-1相关辅活化子(PRC)与PGC-1α具有相同的结构和功能，被认为调节多种代谢途径以及线粒体的生物发生。它参与了细胞增殖的早期编程，表明线粒体功能和细胞周期状态之间存在着精细调控的串扰。在一个来源于线粒体丰富的肿瘤的细胞系模型中探索了PRC调节的途径，该肿瘤本质上是氧化代谢的，尤其是PRC的高表达。在时间PRC抑制条件下，将线粒体的功能状态与基因芯片分析的结果进行比较。为了明确PRC的精细调控，我们用实时定量聚合酶链式反应和蛋白质印迹技术研究了参与氧化磷酸化过程的基因和蛋白的表达水平。与早期对pGC-1α的研究一样，我们研究了一氧化氮在PRC调控的线粒体生物发生中的作用，并确定了它在控制丝裂原活化蛋白激酶途径的磷酸化状态中的作用。我们发现，一氧化氮在转录水平上迅速影响PRC的表达。着眼于线粒体的能量代谢，我们观察到PRC以时间依赖的方式差异地控制呼吸链复合体和偶联效率，以维持线粒体的动态平衡。我们的结果强调了PRC在快速调节代谢功能以响应细胞周期状态方面的关键作用。
The PGC-1 related coactivator (PRC), which shares structural and functional features with PGC-1α, is believed to regulate several metabolic pathways as well as mitochondrial biogenesis. Its involvement in the early programming of cell proliferation suggests the existence of finely regulated crosstalk between mitochondrial functions and the cell cycle status. PRC-regulated pathways were explored in a cell-line model derived from mitochondrial-rich tumours with an essentially oxidative metabolism and specifically high PRC expression. The functional status of mitochondria was compared to the results of microarray analysis under conditions of temporal PRC inhibition. To specify the fine PRC regulation, the expression levels of the genes and proteins involved in the oxidative phosphorylation process were studied by real time quantitative PCR and western blotting. As in earlier studies on PGC-1α, we investigated the role of nitric oxide in PRC-regulated mitochondrial biogenesis and determined its action in the control of the phosphorylation status of the mitogen-activated protein kinase pathway. We found that nitric oxide rapidly influences PRC expression at the transcriptional level. Focusing on mitochondrial energetic metabolism, we observed that PRC differentially controls respiratory chain complexes and coupling efficiency in a time-dependent manner to maintain mitochondrial homeostasis. Our results highlight the key role of PRC in the rapid modulation of metabolic functions in response to the status of the cell cycle.
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影响因子：
5.8
作者：
Nikiforova, MN;Lynch, RA;Nikiforov, YE
通讯作者：
Nikiforov, YE
DOI：
10.1165/rcmb.2005-0153oc
发表时间：
2006-01-01
影响因子：
6.4
作者：
Barlow, C;Shukla, A;Lounsbury, KM
通讯作者：
Lounsbury, KM
影响因子：
11.4
作者：
Biswas, G;Adebanjo, OA;Avadhani, NG
通讯作者：
Avadhani, NG
影响因子：
64.5
作者：
Lin, JD;Wu, PH;Spiegelman, BM
通讯作者：
Spiegelman, BM
影响因子：
8
作者：
Chen, ZH;Seimiya, H;Tsuruo, T
通讯作者：
Tsuruo, T