Department of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706, USA.
Cell Rep. 2013 Jan 31;3(1):237-45. doi: 10.1016/j.celrep.2012.11.029. Epub 2013 Jan 10.
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.
线粒体是代谢和信号的中心，其内容和功能必须适应不断变化的细胞环境。启动线粒体重构的生物信号以及驱动这种适应性反应的细胞过程在很大程度上还不清楚。为了更好地定义这些系统，我们对正在进行线粒体生物发生的小鼠肌肉细胞进行了匹配的定量基因组和蛋白质组学分析。我们发现，参与细胞铁稳态的蛋白质与这一过程高度协调，细胞铁耗竭会导致选定的线粒体蛋白质水平和氧化能力迅速、剂量依赖性下降。我们进一步表明，这个过程在广泛的细胞类型中是普遍存在的，并且当铁重新引入时可以完全逆转。总的来说，我们的工作表明细胞铁是线粒体生物发生的关键调节剂，并提供了可用于探索对线粒体适应至关重要的转录后和翻译后过程的定量数据集。
