小柯机器人

Na+通过线粒体呼吸链调控缺氧信号
2020-07-30 14:30

西班牙圣琼德鲁斯大学医院Antonio Martínez-Ruiz团队发现,Na+通过线粒体呼吸链调控缺氧信号。2020年7月29日出版的《自然》在线发表了这项成果。

研究人员发现Na +可以作为第二信使,通过调控线粒体内膜的流动性来调节氧化磷酸化(OXPHOS)的功能和活性氧的产生。急性缺氧期时线粒体复合体I的构象变化会导致基质酸化,并从磷酸钙(CaP)沉淀物中释放出游离的Ca2+。线粒体Na+/ Ca2+交换体的活化促进了Na+进入基质。Na+与磷脂相互作用降低了线粒体内膜的流动性和复合物II与复合物III之间游离泛醌的迁移率,但不影响超复合物内部的迁移率。因此,在复合物III处产生了超氧化物。

通过Na+/ Ca2+交换体对Na+进口抑制足以阻断该途径,从而阻碍细胞适应缺氧环境。这些结果表明,Na+通过与磷脂先前未知的相互作用来调控OXPHOS功能和氧化还原信号的传导,这对细胞代谢具有深远影响。

据介绍,所有后生动物都依赖于线粒体OXPHOS通过消耗O2来产生能量。此外,OXPHOS利用O2产生可促进细胞适应性的活性氧,这种现象发生在缺氧情况下,但其确切的机理尚不清楚。Ca2+是作为第二信使最典型的离子,但目前所知Na+的功能仅仅是充当膜电位的介体。

附:英文原文

Title: Na + controls hypoxic signalling by the mitochondrial respiratory chain

Author: Pablo Hernansanz-Agustn, Carmen Choya-Foces, Susana Carregal-Romero, Elena Ramos, Tamara Oliva, Tamara Villa-Pia, Laura Moreno, Alicia Izquierdo-lvarez, J. Daniel Cabrera-Garca, Ana Corts, Ana Victoria Lechuga-Vieco, Pooja Jadiya, Elisa Navarro, Esther Parada, Alejandra Palomino-Antoln, Daniel Tello, Rebeca Acn-Prez, Juan Carlos Rodrguez-Aguilera, Plcido Navas, ngel Cogolludo, Ivn Lpez-Montero, lvaro Martnez-del-Pozo, Javier Egea, Manuela G. Lpez, John W. Elrod, Jess Ruz-Cabello, Anna Bogdanova, Jos Antonio Enrquez, Antonio Martnez-Ruiz

Issue&Volume: 2020-07-29

Abstract: All metazoans depend on the consumption of O2 by the mitochondrial oxidative phosphorylation system (OXPHOS) to produce energy. In addition, the OXPHOS uses O2 to produce reactive oxygen species that can drive cell adaptations1,2,3,4, a phenomenon that occurs in hypoxia4,5,6,7,8 and whose precise mechanism remains unknown. Ca2+ is the best known ion that acts as a second messenger9, yet the role ascribed to Na+ is to serve as a mere mediator of membrane potential10. Here we show that Na+ acts as a second messenger that regulates OXPHOS function and the production of reactive oxygen species by modulating the fluidity of the inner mitochondrial membrane. A conformational shift in mitochondrial complex I during acute hypoxia11 drives acidification of the matrix and the release of free Ca2+ from calcium phosphate (CaP) precipitates. The concomitant activation of the mitochondrial Na+/Ca2+ exchanger promotes the import of Na+ into the matrix. Na+ interacts with phospholipids, reducing inner mitochondrial membrane fluidity and the mobility of free ubiquinone between complex II and complex III, but not inside supercomplexes. As a consequence, superoxide is produced at complex III. The inhibition of Na+ import through the Na+/Ca2+ exchanger is sufficient to block this pathway, preventing adaptation to hypoxia. These results reveal that Na+ controls OXPHOS function and redox signalling through an unexpected interaction with phospholipids, with profound consequences for cellular metabolism.

DOI: 10.1038/s41586-020-2551-y

Source: https://www.nature.com/articles/s41586-020-2551-y

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

分享到:

0