ArticlePloS one2008
Metabolic dynamics in skeletal muscle during acute reduction in blood flow and oxygen supply to mitochondria: in-silico studies using a multi-scale, top-down integrated model.
Article in PloS one, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 28 citations in OpenAlex.
- Dynamic balance of myoplasmic energetics, redox state and protons in a fast-twitch oxidative glycolytic skeletal muscle fibre.The Journal of physiology · 2026Article
- Integrating simulated and experimental data to identify mitochondrial bioenergetic defects in Parkinson's Disease models.PloS one · 2026Article
- Systems Biology Approaches Toward Understanding Primary Mitochondrial Diseases.Frontiers in genetics · 2019Review
- Voluntary running protects against neuromuscular dysfunction following hindlimb ischemia-reperfusion in mice.Journal of applied physiology (Bethesda, Md. : 1985) · 2019Article
- A need for NAD+ in muscle development, homeostasis, and aging.Skeletal muscle · 2018Review
- Article
- A Green's function method for simulation of time-dependent solute transport and reaction in realistic microvascular geometries.Mathematical medicine and biology : a journal of the IMA · 2016Article
- 5'-AMP activated protein kinase α2 controls substrate metabolism during post-exercise recovery via regulation of pyruvate dehydrogenase kinase 4.The Journal of physiology · 2015Article
- Computational modeling and analysis of iron release from macrophages.PLoS computational biology · 2014Article
- Systems mapping of metabolic genes through control theory.Advanced drug delivery reviews · 2013Article
- NAD(+)/NADH and skeletal muscle mitochondrial adaptations to exercise.American journal of physiology. Endocrinology and metabolism · 2012Review
- Optimality and thermodynamics determine the evolution of transcriptional regulatory networks.Molecular bioSystems · 2012Article
- Molecules in motion: influences of diffusion on metabolic structure and function in skeletal muscle.The Journal of experimental biology · 2011Review
- Silencing of glycolysis in muscle: experimental observation and numerical analysis.Experimental physiology · 2010Article
- Role of NADH/NAD+ transport activity and glycogen store on skeletal muscle energy metabolism during exercise: in silico studies.American journal of physiology. Cell physiology · 2009Article
- Models of muscle contraction and energetics.Drug discovery today. Disease models · 2008Article
- Computational approaches for understanding energy metabolism.Wiley interdisciplinary reviews. Systems biology and medicineReview
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Control mechanisms of cellular metabolism and energetics in skeletal muscle that may become evident in response to physiological stresses such as reduction in blood flow and oxygen supply to mitochondria can be quantitatively understood using a multi-scale computational model. The analysis of dynamic responses from such a model can provide insights into mechanisms of metabolic regulation that may not be evident from experimental studies. For the purpose, a physiologically-based, multi-scale computational model of skeletal muscle cellular metabolism and energetics was developed to describe dynamic responses of key chemical species and reaction fluxes to muscle ischemia. The model, which incorporates key transport and metabolic processes and subcellular compartmentalization, is based on dynamic mass balances of 30 chemical species in both capillary blood and tissue cells (cytosol and mitochondria) domains. The reaction fluxes in cytosol and mitochondria are expressed in terms of a general phenomenological Michaelis-Menten equation involving the compartmentalized energy controller ratios ATP/ADP and NADH/NAD(+). The unknown transport and reaction parameters in the model are estimated simultaneously by minimizing the differences between available in vivo experimental data on muscle ischemia and corresponding model outputs in coupled with the resting linear flux balance constraints using a robust, nonlinear, constrained-based, reduced gradient optimization algorithm. With the optimal parameter values, the model is able to simulate dynamic responses to reduced blood flow and oxygen supply to mitochondria associated with muscle ischemia of several key metabolite concentrations and metabolic fluxes in the subcellular cytosolic and mitochondrial compartments, some that can be measured and others that can not be measured with the current experimental techniques. The model can be applied to test complex hypotheses involving dynamic regulation of cellular metabolism and energetics in skeletal muscle during physiological stresses such as ischemia, hypoxia, and exercise.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.