Coenzyme Q improves mitochondrial and muscle dysfunction caused by CUG expanded repeats in Caenorhabditis elegans.

IF 3.3 3区 生物学 Q2 GENETICS & HEREDITY Genetics Pub Date : 2025-02-05 DOI:10.1093/genetics/iyae208
Joana Teixeira, Anu-Mari Harju, Alaa Othman, Ove Eriksson, Brendan J Battersby, Susana M D A Garcia
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Abstract

Expansion of nucleotide repeat sequences is associated with more than 40 human neuromuscular disorders. The different pathogenic mechanisms associated with the expression of nucleotide repeats are not well understood. We use a Caenorhabditis elegans model that expresses expanded CUG repeats only in cells of the body wall muscle and recapitulate muscle dysfunction and impaired organismal motility to identify the basis by which expression of RNA repeats is toxic to muscle function. Here, we performed 2 consecutive RNA interference screens and uncovered coenzyme Q metabolism and mitochondrial dysfunction as critical genetic modifiers of the motility phenotype. Furthermore, coenzyme Q supplementation reduced the toxic phenotypes, ameliorating the motility impairment and mitochondrial phenotypes. Together our data show how the expression of expanded RNA repeats can be toxic to mitochondrial homeostasis.

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辅酶Q改善秀丽隐杆线虫CUG扩增重复引起的线粒体和肌肉功能障碍。
核苷酸重复序列的扩增与40多种人类神经肌肉疾病有关。与核苷酸重复序列表达相关的不同致病机制尚不清楚。我们使用秀丽隐杆线虫模型,该模型仅在体壁肌肉细胞中表达扩增的CUG重复序列,并概括肌肉功能障碍和机体运动性受损,以确定RNA重复序列表达对肌肉功能有毒的基础。在这里,我们进行了两次连续的RNA干扰筛选,发现辅酶Q代谢和线粒体功能障碍是运动性表型的关键遗传修饰因子。此外,辅酶Q的补充减少了毒性表型,改善了运动障碍和线粒体表型。我们的数据表明,扩增的RNA重复序列的表达对线粒体稳态是有毒的。
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来源期刊
Genetics
Genetics GENETICS & HEREDITY-
CiteScore
6.90
自引率
6.10%
发文量
177
审稿时长
1.5 months
期刊介绍: GENETICS is published by the Genetics Society of America, a scholarly society that seeks to deepen our understanding of the living world by advancing our understanding of genetics. Since 1916, GENETICS has published high-quality, original research presenting novel findings bearing on genetics and genomics. The journal publishes empirical studies of organisms ranging from microbes to humans, as well as theoretical work. While it has an illustrious history, GENETICS has changed along with the communities it serves: it is not your mentor''s journal. The editors make decisions quickly – in around 30 days – without sacrificing the excellence and scholarship for which the journal has long been known. GENETICS is a peer reviewed, peer-edited journal, with an international reach and increasing visibility and impact. All editorial decisions are made through collaboration of at least two editors who are practicing scientists. GENETICS is constantly innovating: expanded types of content include Reviews, Commentary (current issues of interest to geneticists), Perspectives (historical), Primers (to introduce primary literature into the classroom), Toolbox Reviews, plus YeastBook, FlyBook, and WormBook (coming spring 2016). For particularly time-sensitive results, we publish Communications. As part of our mission to serve our communities, we''ve published thematic collections, including Genomic Selection, Multiparental Populations, Mouse Collaborative Cross, and the Genetics of Sex.
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