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Scaf1 promotes respiratory supercomplexes and metabolic efficiency in zebrafish.
EMBO Reports ( IF 6.5 ) Pub Date : 2020-06-04 , DOI: 10.15252/embr.202050287
Carolina García-Poyatos 1, 2 , Sara Cogliati 1, 3 , Enrique Calvo 1 , Pablo Hernansanz-Agustín 1 , Sylviane Lagarrigue 4 , Ricardo Magni 1 , Marius Botos 2 , Xavier Langa 2 , Francesca Amati 4 , Jesús Vázquez 1, 5 , Nadia Mercader 1 , José Antonio Enríquez 1, 6
Affiliation  

The oxidative phosphorylation (OXPHOS ) system is a dynamic system in which the respiratory complexes coexist with super‐assembled quaternary structures called supercomplexes (SC s). The physiological role of SC s is still disputed. Here, we used zebrafish to study the relevance of respiratory SC s. We combined immunodetection analysis and deep data‐independent proteomics to characterize these structures and found similar SC s to those described in mice, as well as novel SC s including III 2 + IV 2, I + IV , and I + III + IV 2. To study the physiological role of SC s, we generated two null allele zebrafish lines for supercomplex assembly factor 1 (scaf1 ). scaf1 −/− fish displayed altered OXPHOS activity due to the disrupted interaction of complexes III and IV . scaf1 −/− fish were smaller in size and showed abnormal fat deposition and decreased female fertility. These physiological phenotypes were rescued by doubling the food supply, which correlated with improved bioenergetics and alterations in the metabolic gene expression program. These results reveal that SC assembly by Scaf1 modulates OXPHOS efficiency and allows the optimization of metabolic resources.

中文翻译:


Scaf1 促进斑马鱼的呼吸超复合物和代谢效率。



氧化磷酸化(OXPHOS)系统是一个动态系统,其中呼吸复合物与称为超复合物(SC)的超组装四级结构共存。 SC 的生理作用仍存在争议。在这里,我们使用斑马鱼来研究呼吸 SC 的相关性。我们结合免疫检测分析和深度数据独立蛋白质组学来表征这些结构,并发现了与小鼠中描述的类似的 SC,以及新的 SC,包括 III 2 + IV 2 、 I + IV 和 I + III 2 + IV 2 。为了研究 SC 的生理作用,我们针对超复合物组装因子 1 ( scaf1 ) 生成了两个无效等位基因斑马鱼系。由于复合物 III 和 IV 的相互作用被破坏, scaf1 −/−鱼表现出改变的 OXPHOS 活性。 scaf1 −/−鱼体型较小,脂肪沉积异常,雌性生育能力下降。这些生理表型通过加倍食物供应来挽救,这与生物能学的改善和代谢基因表达程序的改变相关。这些结果表明 Scaf1 的 SC 组装可调节 OXPHOS 效率并优化代谢资源。
更新日期:2020-07-03
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