线粒体形态学改变与细胞凋亡

近年来,对于线粒体形态学以及其在凋亡过程中的改变和作用的研究打破了传统的观点。正常情况下,线粒体在细胞内相互连接成管网状结构,并发生着频繁的融合与分裂。融合和分裂由一系列蛋白质介导,二者之间的动态平衡维持着线粒体的形态和功能。在细胞凋亡的早期,线粒体融合和分裂失平衡,导致线粒体管网状结构碎裂和嵴的重构,这些改变对线粒体随后的变化以及凋亡的发生具有重要的意义。融合和分裂的蛋白质不仅调控线粒体形态和细胞凋亡过程,也和某些凋亡相关疾病有关。此外,促凋亡的Bcl-2蛋白可能通过改变线粒体的构形来调控凋亡过程。

Dynamics of Mitochondrial Morphology in Apoptosis

Mitochondria play an important role in apoptosis by integrating intrinsic and extrinsic apoptoticsignals and releasing cytochrome c to initiate caspase cascade.In traditional opinions,there are no changes ornonspecific changes of mitochondrial morphology in early stage of apoptosis.With the discovery of frequent mito-chondria fusion and fission in living cells and application of electron tomography plus 3D imaging in cell biology,concept has been renewed in recent years.Mitochondria in cell form a highly interconnected dynamic tubularnetwork and undergo frequent fusion and fission mediated by series of molecules called fusion-fission proteins.Thedynamic balance between fusion and fission maintains mitochondrial morphology and function.Once apoptosis istriggered and the balance is perturbed,mitochondrial tubular network will shift to fragmentation and the cristae willbecome remodeling.These changes are essential for downstream events of apoptosis including cytochrome crelease and caspase cascade.Fusion-fission proteins influence the course of apoptosis via controlling mitochondrialmorphology and ultrastructure,and may be responsible for apoptosis related disease,such as dominant optic atro-phy(DOA) and Charcot-Marie-Tooth neuropathy(CMT) .On the other hand,apoptosis-regulating molecules suchas Bcl-2 family members can also impact mitochondrial morphology.All these evidences imply significance ofmitochondrial morphology in apoptosis and promote mitochondria to a higher position in cell survival and death.