A Persistence Detector for Metabolic Network Rewiring in an Animal
A Persistence Detector for Metabolic Network Rewiring in an Animal
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DOI：
10.1016/j.celrep.2018.12.064
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发表时间：
2019-01-08
期刊：
影响因子：
8.8
通讯作者：
Walhout, Albertha J. M.
中科院分区：
文献类型：
--
作者：
Bulcha, Jote T.;Giese, Gabrielle E.;Walhout, Albertha J. M.
生物系统必须具备防止对虚假环境输入作出不适当反应的机制。秀丽隐杆线虫有两条短链脂肪酸丙酸酯的分解途径：一条经典的维生素B12依赖性途径和一条丙酸酯分流，当维生素B12水平低时使用。当有足够的流量通过经典途径时，分流途径保持关闭，可能会避免产生分流特异性有毒中间体。在这里，我们发现了一个转录调控电路，激活分流基因表达丙酸积累。核激素受体10（NHR-10）和NHR-68在具有AND逻辑门的1型相干前馈回路中一起用作“持续检测器”，以延迟丙酸盐积累时的分流激活，并避免响应于丙酸盐的非持续脉冲的假分流激活。总之，我们的研究结果确定了动物中的持久性检测器，其转录重新连接丙酸代谢以维持稳态。
Biological systems must possess mechanisms that prevent inappropriate responses to spurious environmental inputs. Caenorhabditis elegans has two breakdown pathways for the short-chain fatty acid propionate: a canonical, vitamin B12-dependent pathway and a propionate shunt that is used when vitamin B12 levels are low. The shunt pathway is kept off when there is sufficient flux through the canonical pathway, likely to avoid generating shunt-specific toxic intermediates. Here, we discovered a transcriptional regulatory circuit that activates shunt gene expression upon propionate buildup. Nuclear hormone receptor 10 (NHR-10) and NHR-68 function together as a "persistence detector" in a type 1, coherent feed-forward loop with an AND-logic gate to delay shunt activation upon propionate accumulation and to avoid spurious shunt activation in response to a non-sustained pulse of propionate. Together, our findings identify a persistence detector in an animal, which transcriptionally rewires propionate metabolism to maintain homeostasis.