Metabolism Core

抽象-核心C 维持代谢和氧化还原动态平衡的能力是肌肉健康和退化的核心。 新陈代谢核心将提供独特的最先进的工具来量化改变的新陈代谢和 骨骼肌中的线粒体功能。线粒体功能障碍引起的能量平衡紊乱 一种控制多种细胞过程的关键机制，可能导致肌肉退化，包括 蛋白质合成和降解、收缩功能、E-C偶联和细胞凋亡之间的平衡。这个 新陈代谢核心将提供一种综合的方法来分析新陈代谢和 线粒体功能在骨骼肌功能障碍中的广泛应用。我们已经发展了最先进的技术 工具包括全球和靶向代谢组学、磁共振和光学光谱学，以及 对分离的线粒体和通透性纤维的生化分析将提供极大的改进和 对肌肉生物学有详细的见解，并有能力在分子水平上监控治疗方法。 这一核心的目标是扩大对这些工具和专业知识的访问，以进行实验设计、数据收集、 分析和解释新陈代谢在骨骼肌健康和功能障碍中的作用。目标1 将提供来自骨骼肌的广泛的目标和全球代谢组和脂组分析 活检、韧带和肌腱，以及生物液和相关生物样本。目标2将提供以下状态 在体线粒体容量和质量(ATPmax和P/O)及肌肉能量状态的ART分析 (聚合酶链式反应/三磷酸腺苷和腺苷二磷酸/三磷酸腺苷)。目标3将提供氧化磷酸化的详细生化分析和 通透性肌肉纤维和分离的线粒体中的线粒体氧化应激。这些测量结果 将提供肌肉新陈代谢、线粒体功能和肌肉能量学的综合图景，可以 用于了解在骨骼肌疾病模型中导致保护或病理的机制。 新陈代谢的中心作用连接肌肉生理学的各个方面，将允许这个核心提供一个 力学与器件之间的天然桥梁和提出的定量分析核心 中间。

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.