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Functional role of respiratory supercomplexes in mice: SCAF1 relevance and segmentation of the Qpool.
Science Advances ( IF 11.7 ) Pub Date : 2020-06-24 , DOI: 10.1126/sciadv.aba7509
Enrique Calvo 1 , Sara Cogliati 1, 2 , Pablo Hernansanz-Agustín 1 , Marta Loureiro-López 1 , Adela Guarás 1 , Rafael A Casuso 2 , Fernando García-Marqués 1 , Rebeca Acín-Pérez 1 , Yolanda Martí-Mateos 1 , J C Silla-Castro 1 , Marta Carro-Alvarellos 1 , Jesús R Huertas 2 , Jesús Vázquez 1, 3 , J A Enríquez 1, 4
Affiliation  

Mitochondrial respiratory complexes assemble into supercomplexes (SC). Q-respirasome (III2 + IV) requires the supercomplex assembly factor (SCAF1) protein. The role of this factor in the N-respirasome (I + III2 + IV) and the physiological role of SCs are controversial. Here, we study C57BL/6J mice harboring nonfunctional SCAF1, the full knockout for SCAF1, or the wild-type version of the protein and found that exercise performance is SCAF1 dependent. By combining quantitative data–independent proteomics, 2D Blue native gel electrophoresis, and functional analysis of enriched respirasome fractions, we show that SCAF1 confers structural attachment between III2 and IV within the N-respirasome, increases NADH-dependent respiration, and reduces reactive oxygen species (ROS). Furthermore, the expression of AOX in cells and mice confirms that CI-CIII superassembly segments the CoQ in two pools and modulates CI-NADH oxidative capacity.



中文翻译:


小鼠呼吸超复合物的功能作用:SCAF1 相关性和 Qpool 的分割。



线粒体呼吸复合物组装成超级复合物(SC)。 Q-呼吸体 (III 2 + IV) 需要超复合物组装因子 (SCAF1) 蛋白。该因子在 N-呼吸体 (I + III 2 + IV) 中的作用和 SC 的生理作用存在争议。在这里,我们研究了携带无功能 SCAF1、SCAF1 完全敲除或该蛋白质野生型版本的 C57BL/6J 小鼠,发现运动表现依赖于 SCAF1。通过结合定量数据独立的蛋白质组学、2D Blue 天然凝胶电泳和富集呼吸体组分的功能分析,我们表明 SCAF1 赋予 N-呼吸体内 III 2和 IV 之间的结构连接,增加 NADH 依赖性呼吸,并减少活性氧物种(ROS)。此外,细胞和小鼠中 AOX 的表达证实 CI-CIII 超组装将 CoQ 分割为两个池并调节 CI-NADH 氧化能力。

更新日期:2020-06-25
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