Proteostasis is adaptive: Balancing chaperone holdases against foldases.
Proteostasis is adaptive: Balancing chaperone holdases against foldases.
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DOI：
10.1371/journal.pcbi.1008460
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发表时间：
2020-12
影响因子：
4.3
通讯作者：
Grainger DJ
中科院分区：
文献类型：
--
作者：
de Graff AM;Mosedale DE;Sharp T;Dill KA;Grainger DJ
因为细胞必须适应不同的压力和生长速度，它的蛋白质稳定系统也必须适应。细胞如何检测和调整蛋白质组折叠以适应不同的条件？在这里，我们探索了一个生物物理成本效益原则，即细胞应该保持其蛋白质组尽可能折叠在尽可能低的能量成本。这可以通过分子伴侣平衡折叠酶（其加速折叠）相对于保持酶（其充当停车点）的差异表达来实现。该模型捕获了在老化过程中在生物体内和不同代谢率的生物体中观察到的折叠酶-保持酶比率的变化。这项工作描述了一个简单的生物物理机制，通过该机制，细胞蛋白质稳态适应不断变化的生长环境的需要。细胞必须保持低水平的蛋白质解折叠，以避免有害的结果，如蛋白质聚集，氧化损伤或过早降解。负责这一过程的蛋白质称为伴侣蛋白，主要有两种：消耗ATP的“折叠酶”，帮助客户折叠;不依赖ATP的“保持酶”，保持未折叠的蛋白质，直到折叠酶到达。虽然折叠酶是折叠所必需的，但大量使用它们是昂贵的。考虑到分子伴侣是丰富和昂贵的，细胞在强大的选择压力下找到折叠酶和保持酶的经济组合以维持低水平的未折叠蛋白。然而，目前还不清楚理想的组合是什么，以及它如何随生长条件而变化。通过研究伴侣蛋白功能的玩具模型，并最大限度地减少在不同的蛋白质合成速率折叠的总成本，我们发现，虽然折叠酶是必要的快速增长，保持酶变得越来越有效，在缓慢的增长。出乎意料的是，随着合成的减慢，预计总伴侣蛋白的需求量会增加，这与蠕虫年龄的观察结果以及不同代谢率的物种一致。因此，这项工作提供了一个一般的框架，了解伴侣蛋白质组的要求，在能量最小化原则。
Because a cell must adapt to different stresses and growth rates, its proteostasis system must too. How do cells detect and adjust proteome folding to different conditions? Here, we explore a biophysical cost-benefit principle, namely that the cell should keep its proteome as folded as possible at the minimum possible energy cost. This can be achieved by differential expression of chaperones–balancing foldases (which accelerate folding) against holdases (which act as parking spots). The model captures changes in the foldase-holdase ratio observed both within organisms during aging and across organisms of varying metabolic rates. This work describes a simple biophysical mechanism by which cellular proteostasis adapts to meet the needs of a changing growth environment. Cells must maintain low levels of protein unfolding to avoid deleterious outcomes such as protein aggregation, oxidative damage, or premature degradation. The proteins responsible for this, called chaperones, come in two main varieties: ATP-consuming “foldases” that help clients fold and ATP-independent “holdases” that hold unfolded proteins until a foldase arrives. While foldases are necessary for folding, they are expensive to have in high quantities. Given that chaperones are abundant and costly, cells are under strong selective pressure to find economical combinations of foldases and holdases for maintaining low levels of unfolded protein. Yet, it is presently unclear what the ideal combination is and how it varies with growth conditions. By examining a toy model of chaperone function and minimizing the total cost of folding at different rates of protein synthesis, we find that while foldases are necessary at fast growth, holdases become increasingly effective at slow growth. Unexpectedly, total chaperone requirements were predicted to increase as synthesis slows, consistent with observations across age in worms, as well as across species with varying metabolic rates. This work thus provides a general framework for understanding the chaperone requirements of a proteome in terms of an energy minimization principle.
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影响因子：
8.8
作者：
Dhondt I;Petyuk VA;Cai H;Vandemeulebroucke L;Vierstraete A;Smith RD;Depuydt G;Braeckman BP
通讯作者：
Braeckman BP
DOI：
10.1098/rstb.2011.0405
发表时间：
2013-05-05
期刊：
Philosophical transactions of the Royal Society of London. Series B, Biological sciences
影响因子：
--
作者：
Hilton GR;Hochberg GK;Laganowsky A;McGinnigle SI;Baldwin AJ;Benesch JL
通讯作者：
Benesch JL
影响因子：
8.8
作者：
Brehme M;Voisine C;Rolland T;Wachi S;Soper JH;Zhu Y;Orton K;Villella A;Garza D;Vidal M;Ge H;Morimoto RI
通讯作者：
Morimoto RI
影响因子：
7.8
作者：
Hansen, Malene;Taubert, Stefan;Kenyon, Cynthia
通讯作者：
Kenyon, Cynthia
影响因子：
16
作者：
Fleckenstein, Tilly;Kastenmueller, Andreas;Buchner, Johannes
通讯作者：
Buchner, Johannes