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[转载]来自孙学军科学网博客:线粒体温度高是必然的

已有 1477 次阅读 2021-4-29 09:50 |系统分类:科研笔记|文章来源:转载

http://blog.sciencenet.cn/blog-41174-1055326.html 

线粒体温度高是必然的 精选

已有 8119 次阅读 2017-5-16 21:15 |个人分类:重点推荐|系统分类:海外观察

有一种公认的说法是,线粒体是外来物种,是在某个历史阶段进入细胞内的一种原始细菌,和细胞的关系属于共生关系,帮助细胞能量代谢,消耗氧气,并产生ATP和大量代谢产物,在功能上是细胞内能量工厂。支持这种观点的证据有,线粒体是细胞内唯一依靠分裂进行复制的细胞器,线粒体是唯一拥有独立遗传基因的细胞器,线粒体有自己独立的封闭膜结构,线粒体可以进行跨细胞转移。

最新研究发现,线粒体的温度是超过37度,这说明过去我们的看法有不全面的情况,细胞本身不是一个温度均匀的场所,有的地方比较冷,有的地方比较热。过去我们只了解整体的温度,对不同部位的温度情况并不了解。下一步应该对某些温度比较低的部位进行测量,拿出更准确的细胞内温度地图。

线粒体是高温部位,这里不仅是能量代谢的枢纽,也是自由基产生最重要的部位。氢气作用下,线粒体是否会加速代谢温度增加,还是降低代谢速率,降低温度,这是需要研究的。现在有了这种线粒体温度测定分子,将来一定会有更多学者把线粒体温度作为一种研究指标

这一研究告诉我们,人类对生命的了解仍然比较粗浅,需要研究和观察的内容还有很多。例如我们对细胞内各种蛋白质的结构和调节方式仍然有许多不知道的内容,这也是结构生物学为什么那么热,吸引那么多科学家投入大量精力的原因,从分子层次了解细胞了解机体的功能,仍然是当前科学最重要的研究领域。

正常人体温约为37°C,但正常人体细胞某些部位温度却能高达50°C。在氧气的参与下,人体细胞燃烧营养物质产生能量。与明火燃烧情况不同,细胞能量代谢是一个受控过程,涉及多个生物化学反应步骤,但仍能产生大量热。能量代谢许多能量是保存在ATP这种高能分子中,一部分以热能的形式散发出来。

这比较类似于汽车发动机,燃烧汽油的热能一部分变成驱动汽车的动力,另一部分变成热量散发出来,为了促进热量散发,需要用水作为媒介结合散热器将发动机的热量散发出来。

细胞能量代谢过程发生在细胞内的线粒体中,这里的温度有可能是高于其它部位,但是由于线粒体体积非常小,直径500-1000纳米,长度1000-2000纳米左右,测量线粒体温度一直无法实现。新加坡科学家发明了温度敏感荧光染料,实现了对线粒体温度的测量。过去1年法国国家卫生与医学研究院的Pierre Rustin等借助这种新染料测量了人类细胞内线粒体的温度,结果发现肾脏和皮肤细胞处于38°C时,其内部线粒体能够比细胞其余部分高6°C10°C。论文预印件在线发表于bioRxiv。同样,日本科学家也使用温度敏感荧光染料,发现人类癌细胞线粒体比细胞的其余部分高6°C9°C。相关论文于2月发表。

英国伦敦大学学院生物化学家Nick Lane表示,这个发现令人吃惊,但又符合逻辑。“线粒体是主要的热源,必须比身体其他部分更热。但我从来没想到过会这么热。”

该发现将对生物学界产生巨大影响。Rustin团队表示,如果动物的线粒体确实是在更高温度下运行,那么生物学家之前在体温下做的实验结果可能都不准确。研究人员还表示,植物和冷血动物体内的线粒体温度可能较低,但还需要进一步研究。

由于线粒体为细胞提供能量,因此线粒体遗传问题可能导致新生儿患上严重疾病,甚至死亡。但目前科学家已经能通过替换胚胎中的线粒体防治此类疾病。

原文检索:

MitochondriaAre Physiologically Maintained At Close To 50 C



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https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5784887/


PLoS Biol. 2018 Jan; 16(1): e2003992.Published online 2018 Jan 25. doi: 10.1371/journal.pbio.2003992PMCID: PMC5784887PMID: 29370167

Mitochondria are physiologically maintained at close to 50 °C

Dominique Chrétien, Conceptualization, Investigation, Methodology,1,2 Paule Bénit, Conceptualization, Investigation, Methodology,1,2 Hyung-Ho Ha, Investigation,3 Susanne Keipert, Investigation,4 Riyad El-Khoury, Investigation, Resources,5 Young-Tae Chang, Conceptualization, Investigation, Writing – review & editing,6Martin Jastroch, Investigation, Writing – original draft, Writing – review & editing,4 Howard T. Jacobs, Conceptualization, Investigation, Methodology, Writing – original draft, Writing – review & editing,7,8 Pierre Rustin, Conceptualization, Funding acquisition, Investigation, Methodology, Supervision, Writing – original draft, Writing – review & editing,1,2,9,* and Malgorzata Rak, Conceptualization, Investigation, Writing – original draft, Writing – review & editing1,2,9Nick Lane, Academic EditorAuthor information Article notes Copyright and License information DisclaimerSee "Hot mitochondria?" in volume 16, e2005113.See "Caveat Pre-Emptor: Contextualising peer review and publication" in volume 17, e3000234.This article has been cited by other articles in PMC.

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Abstract

In endothermic species, heat released as a product of metabolism ensures stable internal temperature throughout the organism, despite varying environmental conditions. Mitochondria are major actors in this thermogenic process. Part of the energy released by the oxidation of respiratory substrates drives ATP synthesis and metabolite transport, but a substantial proportion is released as heat. Using a temperature-sensitive fluorescent probe targeted to mitochondria, we measured mitochondrial temperature in situ under different physiological conditions. At a constant external temperature of 38 °C, mitochondria were more than 10 °C warmer when the respiratory chain (RC) was fully functional, both in human embryonic kidney (HEK) 293 cells and primary skin fibroblasts. This differential was abolished in cells depleted of mitochondrial DNA or treated with respiratory inhibitors but preserved or enhanced by expressing thermogenic enzymes, such as the alternative oxidase or the uncoupling protein 1. The activity of various RC enzymes was maximal at or slightly above 50 °C. In view of their potential consequences, these observations need to be further validated and explored by independent methods. Our study prompts a critical re-examination of the literature on mitochondria.

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Author summary

To ensure a stable internal temperature, endothermic species make use of the heat released during the final steps of food burning by the mitochondria present in all cells of the organism. Indeed, only a fraction of the energy released by the oxidation of respiratory substrates is used to generate ATP, while a substantial proportion is released as heat. Using a temperature-sensitive fluorescent probe targeted to mitochondria, we measured the temperature of active mitochondria in cultured intact human cells. Mitochondria were found to be more than 10 °C warmer when the respiratory chain was functional. This differential was abolished in cells depleted of mitochondrial DNA or by respiratory inhibitors but preserved or enhanced by the expression of thermogenic enzymes such as Ciona 




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