Science:DNA出逃!科学家捕捉到引发自身免疫疾病的“流氓分子”

2018-02-25 佚名 中国生物技术网

一个国际研究团队发现了能够改变身体对濒死细胞反应的过程,并将这个实时瞬间拍摄下来。重要的是,这个被他们称为“大逃亡”的瞬间也许是关节炎等自身免疫性疾病的关键触发因素。

一个国际研究团队发现了能够改变身体对濒死细胞反应的过程,并将这个实时瞬间拍摄下来。重要的是,这个被他们称为“大逃亡”的瞬间也许是关节炎等自身免疫性疾病的关键触发因素。

这个由莫纳什大学生物医学发现研究所(BDI)的Benjamin Kile教授领导的团队发现并记录下在细胞凋亡过程中DNA从线粒体(产生能量的细胞器)中逃离出来的瞬间。这项研究2月23日在线发表在《Science》上。



线粒体是真正的“双重间谍”,它们对于维持细胞生存来说是必不可少的,但是如果它们受损,就会引起导致严重后果的免疫反应。由于线粒体DNA(mtDNA)和细菌DNA拥有共同的祖先,它们也就有着非常多的相似性,所以身体会把出现在线粒体外,或者说是细胞外的mtDNA当作入侵的病原体来对待。这种无法分辨“本体”和“外体”的情况就是造成炎症疾病和自身免疫疾病的原因。

虽然mtDNA的释放被认为是导致自身免疫疾病(比如狼疮)的原因,但是mtDNA是如何从线粒体中逃脱出来却从未被清楚地解释过。BDI的研究人员Kate McArthur博士使用一种革命性的新型显微镜捕捉到线粒体形成“疝气”的瞬间,这个“疝气”会鼓出线粒体,将DNA驱赶到细胞的其他部分。

观察活体细胞的晶格层光显微镜(LLSM)系统是由诺贝尔奖获得者Eric Betzig开发的一种新型技术。它使得科学家们能够以极高的分辨率观察活体细胞。McArthur博士在2015至2017年间多次去Janelia研究园,她还记得第一次观察到线粒体主动地排出自己的DNA。

她说:“作为科学,我们被教育看到某些不可思议的事情时要保持怀疑态度,所以我最初的反应是,‘绝不可能’。”

McArthur博士说:“只有在我认真地多次重复实验之后,我才开始意识到我发现了什么。”

根据Kile教授的说法,当细胞自杀(人体控制血细胞数量平衡的正常过程)时,两种名为BAK和BAX的蛋白质会被触发。

Kile教授说:“我们实时地观察到,这些专业的杀手蛋白在线粒体的外膜上打开了一个巨大的孔隙,导致包括mtDNA在内的线粒体内部物质离开线粒体。BAK和BAX的目的是给濒死的细胞致命一击。但是在这个过程中,mtDNA从线粒体中被释放出来。本质上,这是一种附带伤害,如果不适当控制的话,它会触发免疫系统产生病理性炎症。”

莫纳什大学的Titan Krios冷冻电子显微镜,以及Walter和Eliza Hall研究所的新型晶格层光显微镜捕获的图像也证实了这项发现。前者是目前最先进的生物电子显微镜,后者是由Walter和Eliza Hall研究所的动态成像中心定制的。

Kile教授强调说,在这种研究中,很少取得这样的基础性发现,这一发现对我们理解自体免疫疾病和感染具有深远的意义。

原始出处:
Kate McArthur, Lachlan W. Whitehead, John M. Heddleston, et al. BAK/BAX macropores facilitate mitochondrial herniation and mtDNA efflux during apoptosis. Science. Feb 23, 2018.

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    2018-02-27 jichang
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    2018-02-25 天涯183

    非常好的文章.学习了

    0

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    2018-02-25 清风拂面

    谢谢分享学习

    0

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    2018-02-25 周周人

    学习.

    0

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近些年来,液体活检成了癌症领域的宠儿。游离的DNA可以被用来检测癌症。而在近日,液体活检也迎来了自己的重大突破!

J Viral Hepat:采用Paritaprevir/Ombitasvir/Ritonavir, Dasabuvir和Ribavirin等药物治疗HBV和H

一般来说,HBV的DNA升高是较温和的(<20000 IU/ml),然而此研究发现了一例与乙肝病毒再激活相关的肝炎

检查乙肝,两对半就够了,拿这HBV DNA有何用?

大家都晓得,中国是个肝炎大国,查有没得乙肝要做乙肝两对半检查!那乙肝病毒DNA(HBV-DNA)又是啥子东西哦?

J Hepatol:在急性暴发性病毒性肝炎,I型干扰素受体信号延迟了枯否细胞再补充

在VACV感染时,IFNAR触发骨髓细胞,而不是肝细胞,对急性病毒性肝炎具有重要的调节作用。