大鼠骨骼肌线粒体在适应运动训练之前和之后均含有核编码的RNA种类。
Skeletal Muscle Mitochondria Contain Nuclear-Encoded RNA Species Prior to and Following Adaptation to Exercise Training in Rats.
作者信息
Silver Jessica L, Lamon Séverine, Loke Stella, Mazzarino Gisella, Croft Larry, Ziemann Mark, Soria Megan, Wadley Glenn D, Trewin Adam J
机构信息
Institute for Physical Activity and Nutrition, School of Exercise and Nutrition Sciences, Deakin University, Geelong, Victoria, Australia.
School of Exercise and Nutrition Sciences, Deakin University, Geelong, Victoria, Australia.
出版信息
FASEB J. 2025 Jul 15;39(13):e70702. doi: 10.1096/fj.202500157R.
Skeletal muscle mitochondria adaptation to exercise training is mediated by molecular factors that are not fully understood. Mitochondria import over 1000 proteins encoded by the nuclear genome, but the RNA population resident within the organelle is generally thought to be exclusively encoded by the mitochondrial genome. However, recent in vitro evidence suggests that specific nuclear-encoded miRNAs and other noncoding RNAs (ncRNAs) can reside within the mitochondrial matrix. Whether these are present in mitochondria of skeletal muscle tissue, and whether this is affected by endurance training-a potent metabolic stimulus for mitochondrial adaptation-remains unknown. Rats underwent 4 weeks of moderate-intensity treadmill exercise training, then were humanely killed and tissues were collected for molecular profiling. Mitochondria from gastrocnemius skeletal muscle were isolated by immunoprecipitation, further purified, and then the resident RNA was sequenced to assess the mitochondrial transcriptome. Exercise training elicited typical transcriptomic responses and functional adaptations in skeletal muscle, including increased mitochondrial respiratory capacity. We identified 24 nuclear-encoded coding or noncoding RNAs in purified mitochondria, in addition to 50 nuclear-encoded miRNAs that met a specified abundance threshold. Although none were differentially expressed in the exercise vs. control group at FDR < 0.05, exploratory analyses suggested that the abundance of 3 miRNAs was altered (p < 0.05) in mitochondria isolated from trained compared with sedentary skeletal muscle. We report the presence of a specific population of nuclear-encoded RNAs in the mitochondria isolated from rat skeletal muscle tissue, which could play a role in regulating exercise adaptations and mitochondrial biology.
骨骼肌线粒体对运动训练的适应性是由一些尚未完全了解的分子因素介导的。线粒体从核基因组中导入1000多种蛋白质,但是一般认为细胞器内的RNA群体完全由线粒体基因组编码。然而,最近的体外证据表明,特定的核编码微小RNA(miRNA)和其他非编码RNA(ncRNA)可以存在于线粒体基质中。这些是否存在于骨骼肌组织的线粒体中,以及这是否受耐力训练(一种促进线粒体适应的强大代谢刺激)的影响,仍然未知。大鼠进行了4周的中等强度跑步机运动训练,然后被人道处死并收集组织进行分子分析。通过免疫沉淀分离腓肠肌骨骼肌的线粒体,进一步纯化,然后对驻留RNA进行测序以评估线粒体转录组。运动训练在骨骼肌中引发了典型的转录组反应和功能适应性变化,包括线粒体呼吸能力增强。我们在纯化的线粒体中鉴定出24种核编码的编码或非编码RNA,此外还有50种核编码的miRNA达到了指定的丰度阈值。尽管在错误发现率(FDR)<0.05时,运动组与对照组之间没有差异表达,但探索性分析表明,与久坐不动的骨骼肌分离的线粒体中,3种miRNA的丰度发生了改变(p<0.05)。我们报告了从大鼠骨骼肌组织分离的线粒体中存在特定群体的核编码RNA,它们可能在调节运动适应性和线粒体生物学中发挥作用。