亚细胞水平线粒体激光损伤应激后的命运决定机制研究

Mitochondria are highly dynamic organells, and its dynamic variations in shape have been related to function. Variations in mitochondrial morphology are primarily a flux between reticular network of fused mitochondria and a fragmented arrangement. Besides two shapes above, mitochondria can form donut like structure. To explore the relationship between mitochondrial damage and mitophagy, we invotively apply laser damage in mitochondrial researches. Laser lesion not only specificly induced mitochondria damage, but also changed the mitochondrial shapes. The mitochondria in damaged place firstly were broken to fragment, and then fused to donut like structure. Intersetingly, the mitochondria in undamaged place also formed this structure and it was earlier than that in damaged place, which suggested that there was a specific signal pathway for mitochondria damage in cell. We will figure out the detailed mechanism of this signal pathway with mtehords of Molecular biology and Cell biology and explore its physiological significance in cells. Moreover, the important role of mitochondrial abnormity have been determined in pathogenesis of neurodegenerative diseases. Therefore it is necessary to explore the role of this specific mitochondrial signal pathway in neurodegenerative diseases in order to provide new sights for treatment of diseases in future.

线粒体是高度动态变化的细胞器，且它的形态变化与细胞功能是相关的。线粒体的形态主要在网状网络和碎裂形状之间变化。除了上述两种形态外，线粒体还可以形成圆圈样结构。为了探讨线粒体定点损伤与线粒体自噬之间的关系，我们创新性的将激光损伤应用到线粒体研究中。激光切割不仅特异的引起了线粒体损伤，同时也改变了线粒体形态。激光切割后，损伤部位的线粒体先断裂形成碎片，然后融合形成圆圈样结构。有意思的是，未损伤部位的线粒体也形成了这样的结构，且形成时间早于损伤部位的线粒体，这揭示细胞内存在一条特殊的线粒体损伤信号传递系统。我们将利用分子生物学和细胞生物学等方法研究这条信号通路的具体机制，并且探讨其在细胞内的生理意义。此外，研究表明线粒体异常在神经退行性疾病的致病机理中发挥着重要作用。因此，更好的探讨这种特异的线粒体信号传递通路在神经退行性疾病中的作用就显得十分重要，以期为将来的疾病治疗提供新的思路。

线粒体是动态变化的细胞器，它能通过分裂和融合形成不同的形状以适应不同的环境。在一定的压力条件下线粒体能形成圆圈样结构。但是，线粒体形成圆圈样结构的分子机制目前还不清楚。本研究中，我们利用亚激光特异的损伤细胞中线粒体去观察细胞内线粒体信号转导。我们发现，激光照射后细胞内线粒体很快形成了圆圈样结构。有意思的是，圆圈样结构的线粒体形成于未发生激光损伤的部位。激光损伤后细胞胞浆Ca2+水平急剧升高，而抑制胞浆Ca2+则抑制了激光损伤后线粒体形成圆圈样结构。此外，我们还证明细胞内活性氧以及线粒体活性氧水平对激光损伤后线粒体形成圆圈样结构不发挥作用。由于存在EF hand 结构域。RHOT1 能通过感知胞浆中Ca2+变化来介导线粒体形成圆圈样结构。为了应对线粒体急性损伤，线粒体通过快速合成线粒体编码蛋白来应对激光造成的线粒体损伤。