线粒体炫在棕色脂肪产热中的功能及机制研究

棕色脂肪是机体主要的产热器官，它不仅在维持体温中发挥关键作用，而且对于机体的能量代谢平衡必不可少。线粒体炫是我们课题组新发现的单个线粒体的信号事件，它含有多重信号，包括活性氧的瞬时爆发、膜电位的瞬时去极化、基质pH的碱化、NADH/FADH2的快速氧化等，并且在多种生命过程中发挥重要的信号转导作用。本课题将在前期工作基础上，系统性研究线粒体炫在棕色脂肪产热中的功能。我们将从分离的线粒体、培养的细胞、棕色脂肪组织及活体动物多个层次研究线粒体炫在棕色脂肪细胞产热过程中的作用，确定它是否是新形式的产热机制；同时将利用线粒体蛋白质组氧化还原修饰质谱鉴定技术，筛选受线粒体炫氧化还原修饰调控的关键蛋白质，寻找线粒体炫的下游效应靶点分子，解析其长期信号作用机制；进一步我们还将研究线粒体炫所介导的产热在肥胖过程中的作用，为治疗肥胖等代谢疾病提供新靶点、新策略。

As a key organ of the body, the brown adipose tissue is not only essential for maintaining the homeostasis of body temperature, but also critical for balancing energy metabolism. Mitochondrial flash (mitoflash), discovered by our group, is a new form of mitochondrial signaling activity. It contains multiplexed signals, including bursting production of reactive oxygen species, transient depolarization of mitochondrial membrane potential, transient alkalization of matrix pH, and accelerated oxidation of NADH/FADH2. Importantly, mitoflash is closely involved in multiple processes with variable signaling functions. Based on our previous studies, here we will intensively study the role of mitoflash in the thermogenesis of brown adipocytes. In order to demonstrate whether mitoflash represents a novel mechanism of thermogenesis, we will investigate mitoflash activities in isolated mitochondria, cultured brown adipocytes, and brown adipose tissue both ex vivo and in vivo. Meanwhile, we will identify the key down-stream targets modified by mitoflash-induced posttranslational oxidation with profiling mitochondrial proteomic oxidation-reduction. Moreover, we will illustrate the role of mitoflash-mediated thermogenesis in treating obesity. Overall, this project will not only identity the new mechanism of thermogenesis from a new angle, but also provide new targets and strategies for the therapeutics of metabolic diseases.