Program in Systems Biology, University of Massachusetts Medical School, Worcester, MA.
Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA.
Cell. 2013 Mar 28;153(1):253-66. doi: 10.1016/j.cell.2013.02.050.
Expression profiles are tailored according to dietary input. However, the networks that control dietary responses remain largely uncharacterized. Here, we combine forward and reverse genetic screens to delineate a network of 184 genes that affect the C. elegans dietary response to Comamonas DA1877 bacteria. We find that perturbation of a mitochondrial network composed of enzymes involved in amino acid metabolism and the TCA cycle affects the dietary response. In humans, mutations in the corresponding genes cause inborn diseases of amino acid metabolism, most of which are treated by dietary intervention. We identify several transcription factors (TFs) that mediate the changes in gene expression upon metabolic network perturbations. Altogether, our findings unveil a transcriptional response system that is poised to sense dietary cues and metabolic imbalances, illustrating extensive communication between metabolic networks in the mitochondria and gene regulatory networks in the nucleus.
表达谱是根据饮食输入量身定制的。然而，控制饮食反应的网络在很大程度上仍未被描述。在这里，我们结合正向和反向遗传筛选，描绘了一个由 184 个基因组成的网络，这些基因影响秀丽隐杆线虫对 Comamonas DA1877 细菌的饮食反应。我们发现，干扰参与氨基酸代谢和 TCA 循环的酶的线粒体网络会影响饮食反应。在人类中，相应基因的突变会导致氨基酸代谢的先天性疾病，其中大多数可以通过饮食干预来治疗。我们鉴定了几个转录因子（TFs），它们介导代谢网络扰动时基因表达的变化。总的来说，我们的发现揭示了一个转录反应系统，它能够感知饮食线索和代谢失衡，说明线粒体中的代谢网络和核中的基因调控网络之间存在广泛的交流。
