缺氧/复氧对线粒体功能和动力学的调控机制

线粒体是真核生物的重要细胞器,是生成ATP的"能源工厂"。缺氧/复氧引起的线粒体代谢功能紊乱及线粒体结构改变被认为是心脑肾等细胞缺血性损伤的关键病理原因, 然而缺氧/复氧如何引起线粒体形态的变化来调节线粒体功能和细胞功能一直不清楚。我们已经发现缺氧/复氧导致线粒体融合功能的抑制，并呈现出一种特殊的线粒体环状形态- - donut(X Liu et al., Cell Death & Differ)。本项目将从分子，亚细胞器，细胞等不同层次全面研究缺氧/复氧对线粒体功能和线粒体动力学及特殊形态donut的调控机制，包括（1）缺氧/复氧对线粒体功能的调控；（2）缺氧/复氧对线粒体的形态和融合分裂的动力学的调控；（3）线粒体donut的形成机制和意义。本研究将阐述缺氧/复氧对线粒体形态和功能的调控，及两者的作用关系，揭示线粒体对缺氧/复氧的应答机制，可望为细胞缺血-再灌注损伤病理的研究奠定理论基础。

Mitochondria are intracellular organelles that play a critical role in cellular energy production. The hypoxia-reoxygenation-induced abnormalities in mitochondrial metabolic function and the ensuing changes in mitochondrial morphology are widely believed to be important pathogenic factors that underline ischemic cell injury in various tissues, including the brain, kidney and liver. However, the underlying mechanisms that changes in mitochondrial morphology modulate the mitochondrial and cellular function during hypoxia-reoxygenation are unclear. We found that hypoxia-reoxygenation resulted in mitochondrial fusion inhibition and the formation of a special toroidal mitochondrial morphology-donut (X Liu et al.,Cell Death & Differ). Our project will study the mechanism from molecular, subcellular and cellular levels, including (1) the regulation of hypoxia-reoxygenation on mitochondrial function; (2)the regulation of hypoxia-reoxygenation on mitochondrial morphology and mitochondrial fusion-fission dynamics; (3)the mechanism and function of donut formation. This research will demonstrate the regulation mechanism of hypoxia/reoxygenation on mitochondrial morphology and function, and also the relationship between them, rule out the mitochondrial response mechanism to hypoxia/reoxygenation, and lay a novel theoretical foundation of pathological study on ischemia-reperfusion.