Numerical simulation of mitochondrial systems for ATP generation and membrane transport
- 1Research & Development Center, Zeon Corporation
- 2Division of Integrative Nutiriomics and Oncology, Research Center for Advanced Science and Technology, The University of Tokyo
Abstract
Simulating intracellular biochemical reactions remains a significant challenge in mathematical modeling because of the complex interactions among diverse molecular species. The natural number simulation (NNS) framework offers a dynamic approach to simulating these reactions using a novel algorithm based on reaction equations. In this study, we developed a computational cell model incorporating mitochondria to examine key metabolic processes, including glucose uptake, glycolysis, the tricarboxylic acid cycle, and ATP synthesis via the electron transport chain. Substrate transport mediated by membrane proteins, such as pyruvate and nicotinamide adenine dinucleotide transporters, and the electron transport chain, was replicated using simplified reaction equations. The simulation results showed that, with appropriately chosen rate constants, the ATP production rate reached approximately 155 molecules s − 1 per ATP synthase. Sensitivity analysis indicated that the number of mitochondrial phosphate transporters and the rate of phosphate transport into mitochondria strongly influence ATP production. The model also showed that intermittent glucose supply has a minimal impact on ATP production and that the framework is capable of incorporating the effects of deuterium-containing water on ATP synthesis. This framework provides a foundation for future efforts in simulating more detailed metabolic pathways and integrating experimental data.
Related
- Membrane surface geometry is a determinant of mitochondrial electron transfer and cellular adaptation
- Curvature sensing and generation by diverse membrane-tethered polymers can be explained by a unifying physical model
- Hepatocyte Serine Palmitoyltransferase 3 is essential for mitochondrial ceramide homeostasis and electron transport chain function
- Stress-induced recruitment of small heat shock protein 1 at the outer mitochondrial membrane underlies resistance to apoptosis
- Multiscale Quantum-Classical Simulation of Protein Autoproteolysis in a Million-Atom Membrane Environment
BibTeX
@article{sato2026numerical,
title = {{Numerical simulation of mitochondrial systems for ATP generation and membrane transport}},
author = {Takashi Sato and Tsuyoshi Osawa},
journal = {Scientific Reports},
year = {2026},
month = jul,
doi = {10.1038/s41598-026-61463-0},
url = {https://doi.org/10.1038/s41598-026-61463-0},
note = {CC BY},
}
RIS
TY - JOUR
TI - Numerical simulation of mitochondrial systems for ATP generation and membrane transport
AU - Takashi Sato
AU - Tsuyoshi Osawa
PY - 2026
DA - 2026/07/01
JO - Scientific Reports
DO - 10.1038/s41598-026-61463-0
UR - https://doi.org/10.1038/s41598-026-61463-0
AB - Simulating intracellular biochemical reactions remains a significant challenge in mathematical modeling because of the complex interactions among diverse molecular species. The natural number simulation (NNS) framework offers a dynamic approach to simulating these reactions using a novel algorithm based on reaction equations. In this study, we developed a computational cell model incorporating mitochondria to examine key metabolic processes, including glucose uptake, glycolysis, the tricarboxylic acid cycle, and ATP synthesis via the electron transport chain. Substrate transport mediated by membrane proteins, such as pyruvate and nicotinamide adenine dinucleotide transporters, and the electron transport chain, was replicated using simplified reaction equations. The simulation results showed that, with appropriately chosen rate constants, the ATP production rate reached approximately 155 molecules s − 1 per ATP synthase. Sensitivity analysis indicated that the number of mitochondrial phosphate transporters and the rate of phosphate transport into mitochondria strongly influence ATP production. The model also showed that intermittent glucose supply has a minimal impact on ATP production and that the framework is capable of incorporating the effects of deuterium-containing water on ATP synthesis. This framework provides a foundation for future efforts in simulating more detailed metabolic pathways and integrating experimental data.
SN - 2045-2322
ER -