相关实验视频

Updated: Jun 21, 2025

A Murine Model of Dengue Virus-induced Acute Viral Encephalitis-like Disease

A Murine Model of Dengue Virus-induced Acute Viral Encephalitis-like Disease

Published on: April 28, 2019

登革热病毒非结构蛋白3通过损害复合体I功能来抑制线粒体呼吸

Bruna G Sousa^1,2, Nathane C Mebus-Antunes¹, Lorena O Fernandes-Siqueira¹

¹Instituto de Bioquímica Médica Leopoldo de Meis, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.

|July 9, 2024

概括

登革热病毒NS3蛋白质通过直接抑制电子运输系统的关键组成部分I复合体,损害了线粒体呼吸. 这种病毒蛋白酶活性对于在感染期间改变宿主细胞能量生产至关重要.

科学领域:

生物化学生物化学
病毒学病毒学
细胞生物学细胞生物学

背景情况:

登革热病毒 (DENV) 感染影响宿主细胞代谢,但具体的分子机制尚未完全理解.
线粒体功能障碍与DENV病原发生有关,但负责的病毒因素在很大程度上仍未确定.

研究的目的:

研究DENV非结构蛋白3 (NS3) 在调节宿主线粒体呼吸中的作用.
确定NS3是否直接影响电子传输系统 (ETS) 和其组件.

主要方法:

对DENV感染的肝细胞进行蛋白质组学分析,以识别线粒体中的病毒蛋白.
使用孤立的线粒体和重组DENV NS3结构进行生物化学测试,以评估ETS复杂活动.
高分辨率呼吸计测量线粒体呼吸速率.
在分析中预测NS3与线粒体呼吸链子单元的相互作用.

主要成果:

在感染细胞的线粒体中发现了DENV NS3,与ETS宿主蛋白减少有关.
重组NS3蛋白酶域 (NS3pro) 损害了孤立线粒体中的复合体I (CI) 活性,但其他ETS复合体没有.
NS3降低了线粒体呼吸速率,而不影响膜潜力或呼吸泄漏,表明有针对性的CI抑制.
在基分析预测了在小鼠和人类的CI子单元上潜在的NS3裂解部位.

结论:

通过抑制复杂I功能,DENV NS3直接调节线粒体的生物能量.
似乎NS3的蛋白质分解活性是破坏CI功能所必需的.
NS3代表了一个关键的病毒因子,通过向线粒体呼吸来促进DENV诱导的代谢变化.

关键词:

登革热病毒感染者线粒体的新陈代谢非结构蛋白 3 非结构蛋白 3 呼吸系统复杂的呼吸系统.病毒蛋白酶是一种病毒蛋白酶.

更多相关视频

Unveiling Xenobiotic Transport and Effects in Isolated Mitochondria: Insights from Respirometric and Enzymatic Assays

Unveiling Xenobiotic Transport and Effects in Isolated Mitochondria: Insights from Respirometric and Enzymatic Assays

Published on: March 7, 2025

Measuring Dengue Virus RNA in the Culture Supernatant of Infected Cells by Real-time Quantitative Polymerase Chain Reaction

Measuring Dengue Virus RNA in the Culture Supernatant of Infected Cells by Real-time Quantitative Polymerase Chain Reaction

Published on: November 1, 2018

相关概念视频

The Electron Transport Chain

The Electron Transport Chain

The electron transport chain or oxidative phosphorylation is an exothermic process in which free energy released during electron transfer reactions is coupled to ATP synthesis. This process is a significant source of energy in aerobic cells, and therefore inhibitors of the electron transport chain can be detrimental to the cell's metabolic processes.
Inhibitors of the electron transport chain
Rotenone, a widely used pesticide, prevents electron transfer from Fe-S cluster to ubiquinone or Q...

Electron Transport Chain: Complex I and II

Electron Transport Chain: Complex I and II

The mitochondrial electron transport chain (ETC) is the main energy generation system in the eukaryotic cells. However, mitochondria also produce cytotoxic reactive oxygen species (ROS) due to the large electron flow during oxidative phosphorylation. While Complex I is one of the primary sources of superoxide radicals, ROS production by Complex II is uncommon and may only be observed in cancer cells with mutated complexes.
ROS generation is regulated and maintained at moderate levels necessary...

ATP Synthase: Mechanism

ATP Synthase: Mechanism

In animals, the mitochondrial F1F0 ATP synthase is the key protein that synthesizes ATP molecules through a complex catalytic mechanism. While the nuclear genome encodes the majority of ATP synthase subunits, the mitochondrial genome encodes some of the enzyme's most critical components. The formation of this multi-subunit enzyme is a complex multi-step process regulated at the level of transcription, translation, and assembly. Defects in one or more of these steps can result in decreased...

Electron Transport Chain: Complex III and IV

Electron Transport Chain: Complex III and IV

During the electron transport chain, electrons from NADH and FADH2 are first transferred to complexes I and II, respectively. These two complexes then transfer the electrons to ubiquinol, which carries them further to complex III. Complex III passes the electrons across the intermembrane space to Cyt c, which carries them further to complex IV. Complex IV donates electrons to oxygen and reduces it to water. As electrons pass through complexes I, III, and IV, the energy released aids the pumping...

The Supercomplexes in the Crista Membrane

The Supercomplexes in the Crista Membrane

The mitochondrial cristae membrane is the primary site for the oxidative phosphorylation (OXPHOS) process of energy conversion mediated through respiratory complexes I to V. These complexes have been widely studied for decades, and it has been proven that they form supramolecular structures called respiratory supercomplexes (SC). These higher-order complexes may be crucial in maintaining the biochemical structure and improving the physiological activity of the individual complexes while...