线粒体与Weible-Palade小体互作调控其生物发生的作用机制

Weibel-Palade小体（Weibel-Palade body，WPB）是血管内皮细胞特异的分泌型杆状细胞器，含有大量的生物活性分子,受到刺激时快速释放，参与机体凝血、血管生成及炎症反应等多种生理病理过程。线粒体是真核细胞内重要的能量代谢和钙稳态调控场所，并通过直接相互作用调控多种细胞器的生物发生及功能。线粒体与WPB是否有相互作用还不明确。我们的前期工作发现线粒体与WPB在结构上呈现物理性连接，活细胞实验检测到荧光染料从线粒体到WPB的物质交换，采用CCCP抑制线粒体功能可影响WPB的发生。据此我们提出线粒体与WPB之间可能存在物理的相互作用，调节WPB的生物发生和分泌功能。本课题将首先从形态和功能上确定线粒体与WPB的互作，然后进一步揭示线粒体与WPB互作的分子细胞机制，以进一步理解线粒体互作网络及WPB相关疾病的发生机制。

Weibel-Palade bodies (WPBs) are endothelial-specific cigar-shaped secretory organelles which contain a variety of biologically active molecules. These contents inside WPBs could be released rapidly under stimulation and play crucial roles in hemostasis, angiogenesis, and inflammation. Mitochondrion plays a central role in ATP synthesis and intracellular calcium signaling. Physical contacts and multiple function crosstalks between mitochondria and other organelles have been demonstrated. Whether an interorganellar connection exists between mitochondria and WPB is unknown. Our preliminary results showed that mitochondria have physical contacts with WPBs, which may transfer calcium fluorescent dyes from mitochondria to WPB. Furthermore, biogenesis of WPB was compromised when the function of mitochondria was impaired by CCCP treatment. We therefore hypothesize that there exist physical contacts between mitochondria and WPB. These interaction may play an important role in WPB biogenesis and secretion. In this proposal, we aim to determine the morphological and functional interaction between mitochondria and WPBs, and to explore the possible underlying molecular and cellular mechanisms.