Wolframine缺乏伴随着大鼠横纹肌的代谢不灵活

Wolframin deficiency is accompanied with metabolic inflexibility in rat striated muscles.

Keywords：Energy metabolism, Heart, Metabolic inflexibility, Mitochondria, Skeletal muscle, Wolfram syndrome, Wolframin

关键词：能量代谢、心脏、代谢不灵活、线粒体、骨骼肌、Wolfram 综合征、Wolframin

哺乳动物：大鼠
作者：Tepp Kersti , Aid-Vanakova Jekaterina , Puurand Marju , Timohhina Natalja , Reinsalu Leenu , Tein Karin , Plaas Mario , Shevchuk Igor , Terasmaa Anton , Kaambre Tuuli
出版期刊：《Biochemistry and Biophysics Reports》（2022）

Abstract：

The protein wolframin is localized in the membrane of the endoplasmic reticulum (ER), influencing Ca2+ metabolism and ER interaction with mitochondria, but the exact role of the protein remains unclear. Mutations in Wfs1 gene cause autosomal recessive disorder Wolfram syndrome (WS). The first symptom of the WS is diabetes mellitus, so accurate diagnosis of the disease as WS is often delayed. In this study we aimed to characterize the role of the Wfs1 deficiency on bioenergetics of muscles. Alterations in the bioenergetic profiles of Wfs1-exon-5-knock-out (Wfs1KO) male rats in comparison with their wild-type male littermates were investigated using high-resolution respirometry, and enzyme activity measurements. The changes were followed in oxidative (cardiac and soleus) and glycolytic (rectus femoris and gastrocnemius) muscles. There were substrate-dependent alterations in the oxygen consumption rate in Wfs1KO rat muscles. In soleus muscle, decrease in respiration rate was significant in all the followed pathways. The relatively small alterations in muscle during development of WS, such as increased mitochondrial content and/or increase in the OxPhos-related enzymatic activity could be an adaptive response to changes in the metabolic environment. The significant decrease in the OxPhos capacity is substrate dependent indicating metabolic inflexibility when multiple substrates are available.

文章摘要：

wolframin 蛋白定位于内质网 (ER) 膜，影响 Ca 2+代谢和 ER 与线粒体的相互作用，但该蛋白质的确切作用仍不清楚。Wfs1 基因突变导致常染色体隐性遗传病 Wolfram 综合征 (WS)。WS 的首发症状是糖尿病，因此对 WS 疾病的准确诊断常常被延迟。在这项研究中，我们旨在描述 Wfs1 缺乏对肌肉生物能量学的作用。使用高分辨率呼​​吸测定法和酶活性测量研究了 Wfs1-exon-5-knock-out (Wfs1KO) 雄性大鼠与其野生型雄性同窝仔鼠相比的生物能谱变化。氧化（心脏和比目鱼肌）和糖酵解（股直肌和腓肠肌）肌肉的变化也随之而来。Wfs1KO 大鼠肌肉的耗氧率存在底物依赖性变化。在比目鱼肌中，在所有后续途径中，呼吸频率均显着下降。WS 发育过程中肌肉相对较小的变化，例如线粒体含量增加和/或 OxPhos 相关酶活性增加，可能是对代谢环境变化的适应性反应。OxPhos 容量的显着降低取决于底物，表明当多种底物可用时代谢不灵活。

点击链接即可查看和下载文章：https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8918847/pdf/main.pdf

文章题目、关键词与摘要译文仅用于参考。