Metabolism Core

摘要-核心C 维持代谢和氧化还原稳态的能力是肌肉健康和退化的中心。 代谢核心将提供独特的最先进的工具，以量化改变的代谢， 骨骼肌中线粒体的功能。由于线粒体功能障碍导致的能量稳态破坏是 一种控制多种细胞过程的关键机制，可导致肌肉退化，包括 蛋白质合成和降解、收缩功能、E-C偶联和凋亡之间的平衡。的 代谢核心将提供一种综合方法来分析代谢和代谢水平变化的作用， 线粒体功能在骨骼肌功能障碍中的作用。我们开发了最先进的 包括全局和靶向代谢组学、磁共振和光谱学在内的工具，以及 分离的线粒体和透化纤维的生物化学分析，将提供大大改善和 对肌肉生物学的详细了解，以及在分子水平上监测治疗方法的能力。 这个核心的目标是扩大获得这些工具和专业知识的实验设计，数据收集， 分析和解释，以解决代谢在骨骼肌健康和功能障碍中的作用。要求1 将提供广泛的骨骼肌靶向和全局代谢组学和脂质组学分析 活组织检查、韧带和肌腱，以及生物流体和相关生物样本。目标2将提供 本发明分析了体内线粒体的能力和质量（ATP_（max）和P/O）以及肌肉能量状态， (PCr/ATP和ADP/ATP）。目标3将提供氧化磷酸化的详细生化分析， 透化肌纤维和分离的线粒体中的线粒体氧化应激。这些测量 将提供肌肉代谢、线粒体功能和肌肉能量学的综合图像， 用于了解骨骼肌疾病模型中导致保护或病理学的机制。 连接肌肉生理学各个方面的新陈代谢的核心作用将允许该核心提供一个 力学与器件之间的天然桥梁，提出了定量分析的核心 中心

ABSTRACT – Core C The ability to maintain metabolic and redox homeostasis is at the center of muscle health and degeneration. The Metabolism Core will provide access to unique state of the art tools to quantify altered metabolism and mitochondrial function in skeletal muscle. Disruption of energy homeostasis due to mitochondrial dysfunction is a key mechanism controlling diverse cellular processes that can lead to muscle degeneration, including the balance between protein synthesis and degradation, contractile function, E-C coupling, and apoptosis. The Metabolism Core will provide an integrative approach to analyze the role of changes in metabolic and mitochondrial function in skeletal muscle dysfunction to a broad user base. We have developed state of the art tools that include global and targeted metabolomics, magnetic resonance and optical spectroscopy, and biochemical analyses of isolated mitochondria and permeabilized fibers that will provide vastly improved and detailed insights into muscle biology, and an ability to monitor therapeutic approaches at the molecular level. The goal of this core is to expand access to these tools and expertise for experimental design, data collection, analysis, and interpretation to address the role of metabolism in skeletal muscle health and dysfunction. Aim 1 will provide a broad array of targeted and global metabolomic and lipidomic analyses from skeletal muscle biopsy, ligaments and tendons, as well as biofluids and related biological samples. Aim 2 will provide state of the art analyses of in vivo mitochondrial capacty and quality (ATPmax and P/O) and muscle energety state (PCr/ATP and ADP/ATP). Aim 3 will provide detailed biochemical analyses of oxidative phosphorylation and mitochondrial oxidative stress in permeabilized muscle fibers and isolated mitochondria. These measurements will provide an integrated picture of muscle metabolism, mitochondrial function and muscle energetics that can be used to understand the mechanisms leading to protection or pathology in models of skeletal muscle disease. The central role of metabolism connecting all aspects of muscle physiology will allow this Core to provide a natural bridge between between the Mechanics and Devices and Quantitative Analysis Cores of the proposed center.