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Cell:一种新蛋白可通过稳定线粒体嵴防止细胞凋

来源:未知 编辑:admin 发布时间:2017-08-14
Cell:一种新蛋白可通过稳定线粒体嵴防止细胞凋亡

细胞凋亡一个重要的线粒体机制是Bax与bcl-2结合,引起PTP开放,线粒体肿胀,进而导致线粒体形态结构变化,线粒体内的细胞色素C释放到胞浆中,激活caspase家族激酶,从而引发凋亡。

最新发现一种新蛋白OPA1,它虽然不能影响Bax与Bcl-2结合,也不能直接影响Cyt-C释放,但却能稳定线粒体的嵴结构,减轻线粒体的结构破坏,从而减轻细胞凋亡的产生,这是一种全新的细胞凋亡机制。这一研究结果有两篇文章发表在最新一期Cell上。

原文摘要:

OPA1 Controls Apoptotic Cristae Remodeling Independently from Mitochondrial fusion

Mitochondria amplify activation of caspases during apoptosis by releasing cytochrome c and other cofactors. This is accompanied by fragmentation of the organelle and remodeling of the cristae. Here we provide evidence that Optic Atrophy 1 (OPA1), a profusion dynamin-related protein of the inner mitochondrial membrane mutated in dominant optic atrophy, protects from apoptosis by preventing cytochrome c release independently from mitochondrial fusion. OPA1 does not interfere with activation of the mitochondrial “gatekeepers” BAX and BAK, but it controls the shape of mitochondrial cristae, keeping their junctions tight during apoptosis. Tightness of cristae junctions correlates with oligomerization of two forms of OPA1, a soluble, intermembrane space and an integral inner membrane one. The proapoptotic BCL-2 family member BID, which widens cristae junctions, also disrupts OPA1 oligomers. Thus, OPA1 has genetically and molecularly distinct functions in mitochondrial fusion and in cristae remodeling during apoptosis.

Mitochondrial Rhomboid PARL Regulates Cytochrome c Release during Apoptosis via OPA1-Dependent Cristae Remodeling

Rhomboids, evolutionarily conserved integral membrane proteases, participate in crucial signaling pathways. Presenilin-associated rhomboid-like (PARL) is an inner mitochondrial membrane rhomboid of unknown function, whose yeast ortholog is involved in mitochondrial fusion. Parl−/− mice display normal intrauterine development but from the fourth postnatal week undergo progressive multisystemic atrophy leading to cachectic death. Atrophy is sustained by increased apoptosis, both in and ex vivo. Parl−/−cells display normal mitochondrial morphology and function but are no longer protected against intrinsic apoptotic death stimuli by the dynamin-related mitochondrial protein OPA1. Parl−/− mitochondria display reduced levels of a soluble, intermembrane space (IMS) form of OPA1, and OPA1 specifically targeted to IMS complements Parl−/− cells, substantiating the importance of PARL in OPA1 processing. Parl−/− mitochondria undergo faster apoptotic cristae remodeling and cytochrome c release. These findings implicate regulated intramembrane proteolysis in controlling apoptosis.

作者:weiyanjie 点击:

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