Economics of membrane occupancy and respiro-fermentation.
Economics of membrane occupancy and respiro-fermentation.
复制标题
DOI：
10.1038/msb.2011.34
复制
发表时间：
2011-06-21
影响因子：
9.9
通讯作者：
Mahadevan, Radhakrishnan
中科院分区：
文献类型：
--
作者：
Zhuang, Kai;Vemuri, Goutham N.;Mahadevan, Radhakrishnan
关键词：
作者提出，原核生物的代谢从根本上受到可用于蛋白质表达的细胞质膜表面积的限制，并表明这种限制可以解释以前令人困惑的生理现象，包括呼吸发酵。在细菌、酵母菌和癌细胞中，即使存在充足的氧气，也能同时利用有效的呼吸和无效的发酵，这是一个令人困惑的现象。尽管进行了广泛的研究，但这种现象的生物化学基础仍然模糊不清。我们假设葡萄糖转运蛋白和呼吸链蛋白之间对膜空间的竞争（我们称之为膜占用经济学）影响呼吸和发酵。通过在大肠杆菌的基因组尺度代谢模型中引入基于此概念的唯一约束，我们能够模拟呼吸发酵。进一步分析这一限制的影响，发现差异利用的细胞色素和更快的葡萄糖摄取在厌氧条件下比有氧条件下。基于这些模拟，我们提出细菌细胞通过在氧化磷酸化和底物水平磷酸化之间切换来管理其细胞质膜的组成，以保持最佳的ATP生产。这些结果表明，膜占有约束可能是一个基本的细胞代谢和生理约束，并建立了细胞形态和生理之间的直接联系。
The authors propose that prokaryotic metabolism is fundamentally constrained by the cytoplasmic membrane surface area available for protein expression, and show that this constraint can explain previously puzzling physiological phenomena, including respiro-fermentation. The simultaneous utilization of efficient respiration and inefficient fermentation even in the presence of abundant oxygen is a puzzling phenomenon commonly observed in bacteria, yeasts, and cancer cells. Despite extensive research, the biochemical basis for this phenomenon remains obscure. We hypothesize that the outcome of a competition for membrane space between glucose transporters and respiratory chain (which we refer to as economics of membrane occupancy) proteins influences respiration and fermentation. By incorporating a sole constraint based on this concept in the genome-scale metabolic model of Escherichia coli, we were able to simulate respiro-fermentation. Further analysis of the impact of this constraint revealed differential utilization of the cytochromes and faster glucose uptake under anaerobic conditions than under aerobic conditions. Based on these simulations, we propose that bacterial cells manage the composition of their cytoplasmic membrane to maintain optimal ATP production by switching between oxidative and substrate-level phosphorylation. These results suggest that the membrane occupancy constraint may be a fundamental governing constraint of cellular metabolism and physiology, and establishes a direct link between cell morphology and physiology.
登录
查看更多内容
DOI：
10.1073/pnas.0907732106
发表时间：
2009-12-22
影响因子：
11.1
作者：
Phillips, Rob;Milo, Ron
通讯作者：
Milo, Ron
影响因子：
2.9
作者：
Pfeiffer, T;Bonhoeffer, S
通讯作者：
Bonhoeffer, S
影响因子：
2.8
作者：
Jayachandran, G;Görisch, H;Adrian, L
通讯作者：
Adrian, L
影响因子：
9.9
作者：
通讯作者：
--
影响因子：
3.2
作者：
Nikel, Pablo I.;Zhu, Jiangfeng;Bennett, George N.
通讯作者：
Bennett, George N.