Complementary RNA and protein profiling identifies iron as a key regulator of mitochondrial biogenesis.
Complementary RNA and protein profiling identifies iron as a key regulator of mitochondrial biogenesis.
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DOI：
10.1016/j.celrep.2012.11.029
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发表时间：
2013-01-31
期刊：
影响因子：
8.8
通讯作者：
Pagliarini DJ
中科院分区：
文献类型：
--
作者：
Rensvold JW;Ong SE;Jeevananthan A;Carr SA;Mootha VK;Pagliarini DJ
线粒体是新陈代谢和信号传导的中心，其内容和功能必须适应不断变化的细胞环境。启动线粒体重组的生物信号和驱动这种适应性反应的细胞过程在很大程度上是模糊的。为了更好地定义这些系统，我们在小鼠肌肉细胞进行线粒体生物发生时对它们进行了匹配的定量基因组和蛋白质组分析。我们发现参与细胞铁稳态的蛋白质与这一过程高度协调，细胞铁的消耗会导致特定线粒体蛋白质水平和氧化能力的快速、剂量依赖性下降。我们进一步表明，这一过程在多种细胞类型中都是普遍存在的，并且当重新引入铁时，这一过程会完全逆转。总的来说，我们的工作揭示了细胞铁是线粒体生物发生的关键调节剂，并提供了定量数据集，可用于探索对于线粒体适应至关重要的转录后和翻译后过程。
Mitochondria are centers of metabolism and signaling whose content and function must adapt to changing cellular environments. The biological signals that initiate mitochondrial restructuring and the cellular processes that drive this adaptive response are largely obscure. To better define these systems, we performed matched quantitative genomic and proteomic analyses of mouse muscle cells as they performed mitochondrial biogenesis. We find that proteins involved in cellular iron homeostasis are highly coordinated with this process and that depletion of cellular iron results in a rapid, dose-dependent decrease of select mitochondrial protein levels and oxidative capacity. We further show that this process is universal across a broad range of cell types and fully reversed when iron is reintroduced. Collectively, our work reveals that cellular iron is a key regulator of mitochondrial biogenesis, and provides quantitative data sets that can be leveraged to explore posttranscriptional and posttranslational processes that are essential for mitochondrial adaptation.
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影响因子：
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DOI：
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发表时间：
2010-12-06
期刊：
Journal of visualized experiments : JoVE
影响因子：
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作者：
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