Metabolic Response to Iron Deficiency in Saccharomyces cerevisiae
Metabolic Response to Iron Deficiency in Saccharomyces cerevisiae
复制标题
DOI：
10.1074/jbc.m109.091710
复制
发表时间：
2010-05-07
影响因子：
4.8
通讯作者：
Philpott, Caroline C.
中科院分区：
文献类型：
--
作者：
Shakoury-Elizeh, Minoo;Protchenko, Olga;Philpott, Caroline C.
铁是参与许多细胞过程的酶的重要辅因子，但关于铁缺乏对细胞代谢或铁蛋白的影响知之甚少。以前的研究主要集中在缺铁细胞中转录本和蛋白质水平的变化，但这些变化可能并不反映通过代谢途径的运输活性或通量的变化。我们分析了在富铁和贫铁培养基中生长的酵母的代谢组和转录组，以确定当铁的可用性福尔斯下降时，哪些生物合成过程发生了改变。缺铁导致葡萄糖代谢、氨基酸生物合成和脂质生物合成的变化，这些变化是由于特定的铁依赖性酶的缺乏。铁硫蛋白表现出铁辅因子的损失，但氨基酸合成得以维持。麦角固醇和鞘脂生物合成途径在血红素和二铁酶起作用的点上有阻滞，而必需脂肪酸去饱和酶Ole1对铁耗竭有抗性。缺铁细胞表现出大多数铁酶活性的耗竭，但在缺铁期间活性的丧失并不总是破坏代谢。氨基酸稳态是稳健的，但缺铁损害脂质合成，改变细胞膜的性质和功能。
Iron is an essential cofactor for enzymes involved in numerous cellular processes, yet little is known about the impact of iron deficiency on cellular metabolism or iron proteins. Previous studies have focused on changes in transcript and proteins levels in iron-deficient cells, yet these changes may not reflect changes in transport activity or flux through a metabolic pathway. We analyzed the metabolomes and transcriptomes of yeast grown in iron-rich and iron-poor media to determine which bio-synthetic processes are altered when iron availability falls. Iron deficiency led to changes in glucose metabolism, amino acid biosynthesis, and lipid biosynthesis that were due to deficiencies in specific iron-dependent enzymes. Iron-sulfur proteins exhibited loss of iron cofactors, yet amino acid synthesis was maintained. Ergosterol and sphingolipid biosynthetic pathways had blocks at points where heme and diiron enzymes function, whereas Ole1, the essential fatty acid desaturase, was resistant to iron depletion. Iron-deficient cells exhibited depletion of most iron enzyme activities, but loss of activity during iron deficiency did not consistently disrupt metabolism. Amino acid homeostasis was robust, but iron deficiency impaired lipid synthesis, altering the properties and functions of cellular membranes.