Being right on Q: shaping eukaryotic evolution.
Being right on Q: shaping eukaryotic evolution.
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DOI：
10.1042/bcj20160647
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发表时间：
2016-11-15
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影响因子：
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通讯作者：
Speijer D
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作者：
Speijer D
活性氧（ROS）的形成线粒体是一个不完全了解真核生物的过程。我提出了一个动力学模型[BioEssays（2011）33，88-94]，其中通过FADH 2或NADH进入呼吸链的电子之间的比率（F/N比率）是ROS形成的关键决定因素。在葡萄糖分解期间，该比率低，而在脂肪酸分解期间，该比率高（脂肪酸越长，该比率越高），导致更高的ROS水平。因此，（极长链）脂肪酸的分解应该在线粒体中不产生额外的FADH 2的情况下发生。这解释了过氧化物酶体的进化。潜在的ROS增加也可以解释长寿细胞（神经元）中脂肪酸氧化的缺乏以及其他真核生物的适应，如动态超复合物的形成。宿主和内共生体（内共生体）代谢途径的有效组合允许更大种类的底物（具有不同的F/N比）被氧化，但高F/N比增加ROS的形成。这可能导致肉毒碱穿梭，解偶联蛋白和多种抗氧化机制，特别是与脂肪酸氧化有关[BioEssays（2014）36，634-643]。最近的数据过氧化物酶体的演变及其与线粒体，ROS的形成复杂的I在缺血/再灌注损伤，和supercomplex形成调整F/N比的关系强烈支持该模型。我将进一步讨论模型的光线粒体活性氧形成的实验结果。
Reactive oxygen species (ROS) formation by mitochondria is an incompletely understood eukaryotic process. I proposed a kinetic model [BioEssays (2011) 33, 88–94] in which the ratio between electrons entering the respiratory chain via FADH2 or NADH (the F/N ratio) is a crucial determinant of ROS formation. During glucose breakdown, the ratio is low, while during fatty acid breakdown, the ratio is high (the longer the fatty acid, the higher is the ratio), leading to higher ROS levels. Thus, breakdown of (very-long-chain) fatty acids should occur without generating extra FADH2 in mitochondria. This explains peroxisome evolution. A potential ROS increase could also explain the absence of fatty acid oxidation in long-lived cells (neurons) as well as other eukaryotic adaptations, such as dynamic supercomplex formation. Effective combinations of metabolic pathways from the host and the endosymbiont (mitochondrion) allowed larger varieties of substrates (with different F/N ratios) to be oxidized, but high F/N ratios increase ROS formation. This might have led to carnitine shuttles, uncoupling proteins, and multiple antioxidant mechanisms, especially linked to fatty acid oxidation [BioEssays (2014) 36, 634–643]. Recent data regarding peroxisome evolution and their relationships with mitochondria, ROS formation by Complex I during ischaemia/reperfusion injury, and supercomplex formation adjustment to F/N ratios strongly support the model. I will further discuss the model in the light of experimental findings regarding mitochondrial ROS formation.