小柯机器人

科学家鉴定出线粒体钠离子通道
2019-08-22 12:43

意大利帕多瓦大学Diego De Stefani和Rosario Rizzuto研究组合作鉴定出线粒体内的ATP敏感钾通道。相关论文于2019年8月21日在线发表在《自然》上。

研究人员鉴定了位于线粒体中的蛋白质复合物,其介导ATP依赖性钾电流(即mitoKATP)。与其质膜对应物类似,研究人员发现mitoKATP通道由成孔亚基和ATP结合亚基组成,分别被称为MITOK和MITOSUR。MITOK与MITOSUR的体外重建描绘了mitoKATP的主要特性。 MITOK的过表达引发显著的细胞器肿胀,而该亚基的遗传敲除则导致线粒体膜电位的不稳定、内部空间的扩大和氧化磷酸化的减少。在小鼠模型中,MITOK的缺失能够抑制由二氮嗪引起的心脏保护作用。这些结果表明,mitoKATP通道通过调节细胞器的体积和功能来响应细胞的能量状态,从而在线粒体生理学以及在几种病理过程的潜在影响中起关键作用。

据介绍,线粒体以ATP的形式为内源反应提供化学能,它们的活性必须满足细胞能量需求,但是将细胞器性能与ATP水平联系起来的机制却知之甚少。

附:英文原文

Title: Identification of an ATP-sensitive potassium channel in mitochondria

Author: Angela Paggio, Vanessa Checchetto, Antonio Campo, Roberta Menab, Giulia Di Marco, Fabio Di Lisa, Ildiko Szabo, Rosario Rizzuto, Diego De Stefani

Issue&Volume: 2019-08-21

Abstract: Mitochondria provide chemical energy for endoergonic reactions in the form of ATP, and their activity must meet cellular energy requirements, but the mechanisms that link organelle performance to ATP levels are poorly understood. Here we confirm the existence of a protein complex localized in mitochondria that mediates ATP-dependent potassium currents (that is, mitoKATP). We show thatsimilar to their plasma membrane counterpartsmitoKATP channels are composed of pore-forming and ATP-binding subunits, which we term MITOK and MITOSUR, respectively. In vitro reconstitution of MITOK together with MITOSUR recapitulates the main properties of mitoKATP. Overexpression of MITOK triggers marked organelle swelling, whereas the genetic ablation of this subunit causes instability in the mitochondrial membrane potential, widening of the intracristal space and decreased oxidative phosphorylation. In a mouse model, the loss of MITOK suppresses the cardioprotection that is elicited by pharmacological preconditioning induced by diazoxide. Our results indicate that mitoKATP channels respond to the cellular energetic status by regulating organelle volume and function, and thereby have a key role in mitochondrial physiology and potential effects on several pathological processes.

DOI: 10.1038/s41586-019-1498-3

Source:https://www.nature.com/articles/s41586-019-1498-3

Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:43.07
官方网址:http://www.nature.com/
投稿链接:http://www.nature.com/authors/submit_manuscript.html


本期文章:《自然》:Online/在线发表

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