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多胺影响巨噬细胞激活
来源:小柯机器人 发布时间:2019/8/8 9:24:50

德国马克斯·普朗克免疫生与表观研究所的Erika L. Pearce团队发现eIF5A修饰调控线粒体呼吸及巨噬细胞活化。2019年8月,国际知名学术期刊《细胞—代谢》发表了这一成果。

研究人员发现,hypusine修饰的eIF5A (eIF5AH)促进参与TCA循环和氧化磷酸化(OXPHOS)的一系列线粒体蛋白的高效表达。其中一些蛋白质具有线粒体靶向序列(MTS),这在一定程度上增加了对eIF5AH的依赖。在巨噬细胞中,OXPHOS和糖酵解之间的代谢转换支撑了由激活信号引起的不同功能命运。在这些细胞中,eIF5A的修饰似乎在激活后受到动态调控。利用体内和体外模型,研究人员发现,这一途径的急性抑制会削弱OXPHOS依赖的选择性激活,同时保留了有氧糖酵解依赖的经典激活。这些发现对于靶向多胺-eIF5A-hypusine修饰信号轴进行治疗性调控巨噬细胞激活具有借鉴意义。

据了解,细胞如何调整代谢来满足需求是生物学中一个活跃的研究领域。在众多的功能中,需要多胺(亚精胺)来修饰转录因子真核起始因子5A (eIF5A)。

 

附:英文原文

Title: Polyamines and eIF5A Hypusination Modulate Mitochondrial Respiration and Macrophage Activation

Author: Daniel J. Puleston, Michael D. Buck, Ramon I. Klein Geltink, Edward J. Pearce, Stefan Balabanov, Erika L. Pearce

Issue&Volume:  Volume 30 Issue 2

Abstract: How cells adapt metabolism to meet demands is an active area of interest across biology. Among a broad range of functions, the polyamine spermidine is needed to hypusinate the translation factor eukaryotic initiation factor 5A (eIF5A). We show here that hypusinated eIF5A (eIF5AH) promotes the efficient expression of a subset of mitochondrial proteins involved in the TCA cycle and oxidative phosphorylation (OXPHOS). Several of these proteins have mitochondrial targeting sequences (MTSs) that in part confer an increased dependency on eIF5AH. In macrophages, metabolic switching between OXPHOS and glycolysis supports divergent functional fates stimulated by activation signals. In these cells, hypusination of eIF5A appears to be dynamically regulated after activation. Using in vivo and in vitro models, we show that acute inhibition of this pathway blunts OXPHOS-dependent alternative activation, while leaving aerobic glycolysis-dependent classical activation intact. These results might have implications for therapeutically controlling macrophage activation by targeting the polyamine-eIF5A-hypusine axis.

DOI: https://doi.org/10.1016/j.cmet.2019.05.003

Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(19)30243-8

期刊信息

Cell Metabolism:《细胞—代谢》,创刊于2005年。隶属于细胞出版社,最新IF:22.415
官方网址:https://www.cell.com/cell-metabolism/home
投稿链接:https://www.editorialmanager.com/cell-metabolism/default.aspx


本期文章:《细胞—代谢》:Volume 30 Issue 2