Core D: Comparative Mitochondrial Health Assessment Core

正常线粒体功能的维持因生物而异，其氧代谢也不同。 以及对病理生理应激的反应。尽管生物能量学已经被广泛地研究过 老化模型的范围这些参数尚未与控制的措施相结合 线粒体质量和线粒体遗传学。我们已经引入了生物能量健康的概念 翻译研究，现在计划将其扩展到衰老模型。在比较线粒体中 健康评估的核心是生物能量学、线粒体方面的最新技术和成熟的技术 课程内容包括遗传学、自噬和氧化还原生物学。线粒体健康的控制机制 涉及线粒体遗传学、线粒体-核相互作用和有丝分裂。提供给我们的新模式 老龄化社区将是线粒体核交换(MNX)小鼠，它们是在 UAB。这使得特定的线粒体DNA序列在衰老过程中的贡献 与核贡献无关的分摊。最先进的实验设计和协议 评估细胞生物能量学对氧化和代谢应激的反应也将被使用。作为自噬 和有丝分裂吞噬已被证明是健康寿命的关键，而自噬不足有助于 蛋白质聚集和功能障碍的线粒体，自噬通量的指标可以是 量过了。核心的一个重要方面是将这些技术扩展到各种传统物种 从酵母到小鼠，包括冷冻保存的约60种哺乳动物的成纤维细胞 和鸟类，其中许多来自具有特殊生物老生学兴趣的物种，以及活着的物种 对于它们的体型来说，要么特别长寿，要么特别短命，比如短命的鱼，Nothobranchius 弗泽里。具体地说，将向NIA的常规成员和支持成员以及试点和可行性提供服务 获奖者：1.分子能量学分析，包括细胞、细胞器和组织测量， 包括我们在椭圆形细胞结构和复杂的多细胞结构中首创的方法 如胰岛、血管段和脂肪组织，并补充有针对性的方法 代谢组学和氧电极。2.定量氧化应激参数用于评估氧化还原指数 变化包括氧化脂质、硫醇和修饰蛋白质。3.线粒体核交换(MNX) 模型、线粒体DNA损伤和单倍型以测试线粒体DNA序列对生物能量学的独特贡献 以及对新陈代谢和氧化应激的抵抗力，传统的方法既适用于小鼠 整个中心使用的老化模型和比较模型。4.自噬和有丝分裂吞噬 氧化应激和神经变性的病理生物学方面的评估将扩大到 老龄化的模式。5.虚拟和湿法实验室工作坊教育项目。

The maintenance of normal mitochondrial function varies between organisms as does their oxygen metabolism and response to pathophysiological stress. Although bioenergetic metrics have been surveyed in a broad range of aging models these parameters have yet to be integrated with measures of the control of mitochondrial quality and mitochondrial genetics. We have introduced the concept of Bioenergetic health in translational research and now plan to extend this to models of aging. In the Comparative Mitochondrial Health Assessment core both state of the art and established techniques in bioenergetics, mitochondrial genetics, autophagy and redox biology will be offered. The mechanisms controlling mitochondrial health involve mitochondrial genetics, mitochondrial-nuclear interaction and mitophagy. The novel models offered to the aging community will be the mitochondrial nuclear exchange (MNX) mice which have been pioneered at UAB. This allows the contribution of specific mitochondrial DNA sequences to the process of aging to be assessed independent of the nuclear contribution. State of the art experimental design, and protocols for assessing cellular bioenergetics in response to oxidative and metabolic stress will also be used. As autophagy and mitophagy have been shown to be essential for healthy lifespan, and insufficient autophagy contributes to accumulation of protein aggregates and dysfunctional mitochondria, indices of autophagic flux can be measured. An important aspect of the Core is extending these techniques to a variety of traditional species from yeast to mice, including both cryopreserved “cell zoo” of fibroblasts from about 60 species of mammals and birds, a lot of these from species of “exceptional biogerontological interest”, as well as live species that are either exceptionally long-lived or short-lived for their body size, such as the short-lived fish, Nothobranchius furzeri. Specifically, services will be provided to NIA Regular and Supported Members and pilot & feasibility grant awardees in: 1. Molecular energetics analysis including cellular, organelle and tissue measurements, including approaches we have pioneered in spheroid like cell structures and complex multi-cellular structures such as pancreatic islets, vessel segments and adipose tissue, and complementing approaches with targeted metabolomics and oxygen electrodes. 2. Quantitative oxidative stress parameters to assess indices of redox changes including oxidized lipids, thiols and modified proteins. 3. Mitochondrial nuclear exchange (MNX) models, mtDNA damage and haplotyping to test the unique contribution of mtDNA sequences to bioenergetics and the resistance to metabolic and oxidative stress, with approaches available for both the traditional murine models and comparative models of aging used throughout the Center. 4. Autophagy and mitophagy assessments in the context of the pathobiology of oxidative stress and neurodegeneration will be extended to the models of aging. 5. Virtual and wet lab workshop educational programs.