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Macrophage mitochondrial bioenergetics and tissue invasion are boosted by an Atossa-Porthos axis in Drosophila
The EMBO Journal ( IF 9.4 ) Pub Date : 2022-03-23 , DOI: 10.15252/embj.2021109049
Shamsi Emtenani 1 , Elliot T Martin 2 , Attila Gyoergy 1 , Julia Bicher 1 , Jakob-Wendelin Genger 3 , Thomas Köcher 4 , Maria Akhmanova 1 , Mariana Guarda 1 , Marko Roblek 1 , Andreas Bergthaler 3 , Thomas R Hurd 5 , Prashanth Rangan 2 , Daria E Siekhaus 1
Affiliation  

Cellular metabolism must adapt to changing demands to enable homeostasis. During immune responses or cancer metastasis, cells leading migration into challenging environments require an energy boost, but what controls this capacity is unclear. Here, we study a previously uncharacterized nuclear protein, Atossa (encoded by CG9005), which supports macrophage invasion into the germband of Drosophila by controlling cellular metabolism. First, nuclear Atossa increases mRNA levels of Porthos, a DEAD-box protein, and of two metabolic enzymes, lysine-α-ketoglutarate reductase (LKR/SDH) and NADPH glyoxylate reductase (GR/HPR), thus enhancing mitochondrial bioenergetics. Then Porthos supports ribosome assembly and thereby raises the translational efficiency of a subset of mRNAs, including those affecting mitochondrial functions, the electron transport chain, and metabolism. Mitochondrial respiration measurements, metabolomics, and live imaging indicate that Atossa and Porthos power up OxPhos and energy production to promote the forging of a path into tissues by leading macrophages. Since many crucial physiological responses require increases in mitochondrial energy output, this previously undescribed genetic program may modulate a wide range of cellular behaviors.

中文翻译:

果蝇中的阿托萨-波托斯轴促进巨噬细胞线粒体生物能量学和组织侵袭

细胞代谢必须适应不断变化的需求以实现体内平衡。在免疫反应或癌症转移期间,导致迁移到具有挑战性的环境中的细胞需要能量提升,但控制这种能力的因素尚不清楚。在这里,我们研究了一种以前未被表征的核蛋白 Atossa(由CG9005编码),它通过控制细胞代谢来支持巨噬细胞侵入果蝇的种带。首先,核 Atossa 增加了 Porthos(一种 DEAD-box 蛋白)和两种代谢酶赖氨酸-α-酮戊二酸还原酶 (LKR/SDH) 和 NADPH 乙醛酸还原酶 (GR/HPR) 的 mRNA 水平,从而增强了线粒体生物能量学。然后 Porthos 支持核糖体组装,从而提高 mRNA 子集的翻译效率,包括影响线粒体功能、电子传递链和新陈代谢的 mRNA。线粒体呼吸测量、代谢组学和实时成像表明,Atossa 和 Porthos 增强了 OxPhos 和能量产生,以促进引导巨噬细胞形成进入组织的路径。由于许多重要的生理反应需要增加线粒体能量输出,
更新日期:2022-03-23
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