Mechanisms linking mitochondrial form and function

摘要 线粒体是内共生细胞器，并保留了减少的基因组 每个细胞包装成100-1000个核样拷贝，分布在动态 线粒体“合胞体”。线粒体是真核细胞的代谢中心，产生 通过氧化磷酸化和其他关键构件的ATP。它们已经进化到 动态行为，成为一个集成的装配和调节平台 信号通路，如细胞死亡和先天免疫。鉴于它们的核心作用，它是 不足为奇的是，线粒体功能障碍与越来越大的 人类遗传性疾病和常见疾病的比例，如 神经退行性疾病、代谢综合征和癌症。要深入了解 线粒体在疾病和健康中的作用，我们关注的是线粒体如何 行为在细胞内受到控制，以及这种行为是如何与新陈代谢和 细胞行为。我们目前的研究解决了悬而未决的问题，即 线粒体DNA拷贝数和传递在细胞中是如何控制的 线粒体内膜分化为不同的结构域以及线粒体是如何 行为、新陈代谢和细胞行为是一体的。解决这些问题将 阐明线粒体如何促进细胞动态平衡和发病机制。

Summary Mitochondria are endosymbiotic organelles and have retained a reduced genome packaged into 100-1000 copies of nucleoids per cell, distributed within dynamic mitochondria “syncytia”. Mitochondria are the metabolic hubs of eukaryotic cells, producing ATP via oxidative phosphorylation and other critical building blocks. They have evolved to behave dynamically and to be an integrating platform for the assembly and regulation of signaling pathways, such as cell death and innate immunity. Given their central roles, it is not surprising that that mitochondrial dysfunction is associated with an increasingly large proportion of human inherited disorders and with common diseases, such as neurodegenerative disorders, metabolic syndromes, and cancer. To gain insight into the roles of mitochondria in sickness and in health, we are focused on how mitochondrial behavior is controlled within cells and how this behavior is intertwined with metabolism and cell behavior. Our current research addresses the outstanding questions of how mitochondrial DNA copy number and transmission is controlled in cells, how the mitochondrial inner membrane is differentiated into distinct domains and how mitochondrial behavior, metabolism and cell behavior are integrated. Addressing these questions will illuminate how mitochondria contribute to cellular homeostasis and pathogenesis.