The role of mitochondria in mediating or moderating disturbances in oxidative metabolism

线粒体在介导或调节氧化代谢紊乱中的作用

• 批准号: RGPIN-2018-06052
• 负责人: Treberg, Jason
• 金额: $ 2.91万
• 依托单位: University of Manitoba
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2020
• 资助国家: 加拿大
• 起止时间: 2020-01-01 至 2021-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=714054
• 关键词: role; mitochondria; mediating; moderating; disturbances

My research program is focused on investigating metabolism to better understand how environmental stressors can impact wild fish with a focus on mitochondrial processes. To achieve this aim, my work follows 3 main themes that separate along differing levels of biological organization; from 1) in vitro development of mechanistic linkages among mitochondrial processes to 2) laboratory experiments linking whole animal responses with mitochondrial function and 3) examination of wild fish from the Experimental Lakes Area (IISD-ELA). Theme 1 will focus on mitochondrial control of hydrogen peroxide levels. Mitochondria are often blamed as a primary source of reactive oxygen species (ROS), the overproduction of which can lead to oxidative stress. This theme will use isolated mitochondria as the primary study system starting with representative endotherms (rodents) and then expanding to include representative ectotherms to evaluate if my lab's current model of mitochondria as regulators of ROS may have broad phylogenetic and physiological relevance. Theme 2 will evaluate the relationship between cellular oxidative metabolism and individual variation in responses to thermal challenge. This will combine hypotheses linking oxidative stress with elevated growth, mitochondrial efficiency and metabolic rate and the detrimental impacts of heat challenge. The study will involve fish of the genus Salvelinus (for example brook and lake trout), which are native to well-oxygenated, cold waters and may be particularly prone to the negative impacts of warming. Under conditions of thermal challenge, growth dynamics of individual fish will be evaluated to test if larger individuals have a lower tolerance to heat challenge. Metabolic and physiological performance will be evaluated as well and used to validate markers for application in Theme 3. Theme 3 will test for non-lethal means of monitoring metabolic limitation or disruption in wild fishes. This theme will examine how local ecosystem and environmental features impact wild fish metabolism. Lake Trout populate several small lakes in the IISD-ELA that are not interconnected, creating isolated populations. However, the lake environments vary substantial across the ELA, particularly due to fluctuation in temperature and oxygen availability. Using the methodology developed form themes 1 and 2, this theme will integrate metabolic data from the whole animal, mitochondrial function assays (validated in Theme 2) and the molecular level (oxidative stress) to determine if metabolic disruption correlates with these alterations in life-history traits in wild fish. The proposed program would contribute to the training of at least 10 highly qualified personnel from the PhD to undergraduate level. These trainees will develop skills ranging from biochemical analysis to the design and implementation of field-based physiological experiments.

我的研究项目主要集中在研究新陈代谢，以更好地了解环境压力如何影响野生鱼类，重点是线粒体过程。为了实现这一目标，我的工作遵循3个主要主题，分离沿着不同水平的生物组织;从1）线粒体过程之间的机械联系的体外开发到2）将整个动物反应与线粒体功能联系起来的实验室实验和3）来自实验湖区（IISD-ELA）的野生鱼类的检查。 主题1将集中于线粒体对过氧化氢水平的控制。线粒体通常被认为是活性氧（ROS）的主要来源，其过度产生可导致氧化应激。这个主题将使用分离的线粒体作为主要的研究系统，从代表性的内温动物（啮齿动物）开始，然后扩展到包括代表性的外温动物，以评估我的实验室目前的线粒体作为ROS调节因子的模型是否可能具有广泛的系统发育和生理相关性。 主题2将评估细胞氧化代谢与热刺激反应个体差异之间的关系。这将结合联合收割机假设，将氧化应激与升高的生长、线粒体效率和代谢率以及热挑战的有害影响联系起来。这项研究将涉及红点鲑属的鱼类（例如溪鳟和湖鳟），它们原产于含氧良好的寒冷沃茨，可能特别容易受到变暖的负面影响。在热挑战条件下，将评估个体鱼的生长动力学，以测试较大的个体是否对热挑战具有较低的耐受性。还将评估代谢和生理性能，并用于验证主题3中应用的标记物。 主题3将测试监测野生鱼类代谢限制或破坏的非致命手段。这个主题将研究当地生态系统和环境特征如何影响野生鱼类的新陈代谢。湖鳟鱼居住在IISD-ELA的几个小湖泊中，这些湖泊没有相互连接，形成了孤立的种群。然而，整个ELA的湖泊环境差异很大，特别是由于温度和氧气供应的波动。使用从主题1和2开发的方法，本主题将整合来自整个动物的代谢数据，线粒体功能测定（在主题2中验证）和分子水平（氧化应激），以确定代谢中断是否与野生鱼类生活史特征的这些改变相关。 拟议的方案将有助于至少10个高素质的人才从博士到本科水平的培训。这些学员将发展从生化分析到设计和实施实地生理实验的技能。