Research School of Biology, Australian National University, Canberra, ACT, Australia.
Division of Genome Science and Cancer, ACRF INCITe Centre - ANU Node, John Curtin School of Medical Research, Australian National University, Canberra, ACT, Australia.
Nat Commun. 2021 Sep 6;12(1):5282. doi: 10.1038/s41467-021-25563-x.
Homeostasis is one of the fundamental concepts in physiology. Despite remarkable progress in our molecular understanding of amino acid transport, metabolism and signaling, it remains unclear by what mechanisms cytosolic amino acid concentrations are maintained. We propose that amino acid transporters are the primary determinants of intracellular amino acid levels. We show that a cell's endowment with amino acid transporters can be deconvoluted experimentally and used this data to computationally simulate amino acid translocation across the plasma membrane. Transport simulation generates cytosolic amino acid concentrations that are close to those observed in vitro. Perturbations of the system are replicated in silico and can be applied to systems where only transcriptomic data are available. This work explains amino acid homeostasis at the systems-level, through a combination of secondary active transporters, functionally acting as loaders, harmonizers and controller transporters to generate a stable equilibrium of all amino acid concentrations.
稳态是生理学中的基本概念之一。尽管我们在氨基酸运输、代谢和信号转导的分子理解方面取得了显著进展，但细胞内氨基酸浓度是如何维持的仍不清楚。我们提出氨基酸转运体是细胞内氨基酸水平的主要决定因素。我们表明，细胞内氨基酸转运体的丰度可以通过实验进行解析，并利用这些数据对氨基酸穿过质膜的转运进行计算模拟。转运模拟产生的细胞内氨基酸浓度与体外观察到的非常接近。在计算机中复制系统的干扰，并可应用于仅提供转录组数据的系统。这项工作通过组合功能上作为加载器、协调器和控制器转运体的继发性主动转运体，从系统水平上解释了氨基酸稳态，以生成所有氨基酸浓度的稳定平衡。
