Voorsluijs Valérie, Avanzini Francesco, Falasco Gianmaria, Esposito Massimiliano, Skupin Alexander
Luxembourg Centre for Systems Biomedicine, University of Luxembourg, 6 avenue du Swing, 4367 Belvaux, Luxembourg.
Complex Systems and Statistical Mechanics, Department of Physics and Materials Science, University of Luxembourg, 162 A avenue de la Faïencerie, 1511 Luxembourg, Luxembourg.
iScience. 2024 Feb 1;27(3):109078. doi: 10.1016/j.isci.2024.109078. eCollection 2024 Mar 15.
Energy transduction is central to living organisms, but the impact of enzyme regulation and signaling on its thermodynamic efficiency is generally overlooked. Here, we analyze the efficiency of ATP production by the tricarboxylic acid cycle and oxidative phosphorylation, which generate most of the chemical energy in eukaryotes. Calcium signaling regulates this pathway and can affect its energetic output, but the concrete energetic impact of this cross-talk remains elusive. Calcium enhances ATP production by activating key enzymes of the tricarboxylic acid cycle while calcium homeostasis is ATP-dependent. We propose a detailed kinetic model describing the calcium-mitochondria cross-talk and analyze it using nonequilibrium thermodynamics: after identifying the effective reactions driving mitochondrial metabolism out of equilibrium, we quantify the mitochondrial thermodynamic efficiency for different conditions. Calcium oscillations, triggered by extracellular stimulation or energy deficiency, boost the thermodynamic efficiency of mitochondrial metabolism, suggesting a compensatory role of calcium signaling in mitochondrial bioenergetics.
能量转导是生物体的核心，但酶调节和信号传导对其热力学效率的影响通常被忽视。在这里，我们分析了三羧酸循环和氧化磷酸化产生ATP的效率，这两种过程在真核生物中产生了大部分化学能。钙信号调节这一途径，并可能影响其能量输出，但这种相互作用的具体能量影响仍不清楚。钙通过激活三羧酸循环的关键酶来增强ATP的产生，而钙稳态则依赖于ATP。我们提出了一个详细的动力学模型来描述钙 - 线粒体的相互作用，并使用非平衡热力学对其进行分析：在确定驱动线粒体代谢偏离平衡的有效反应后，我们量化了不同条件下线粒体的热力学效率。由细胞外刺激或能量缺乏引发的钙振荡提高了线粒体代谢的热力学效率，表明钙信号在线粒体生物能量学中具有补偿作用。
