On paradoxes between optimal growth, metabolic control analysis, and flux balance analysis

Westerhoff, Hans V.

doi:10.1016/j.biosystems.2023.104998

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2024

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Cited by 2 publications

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50 years of Metabolic Control Analysis: Its past and current influence in the biological sciences

Fell,

Saavedra,

Rohwer

2024

BioSystems

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50 years of Metabolic Control Analysis: Its past and current influence in the biological sciences

Fell,

Saavedra,

Rohwer

2024

BioSystems

View full text Add to dashboard Cite

MitoMAMMAL: a genome scale model of mammalian mitochondria predicts cardiac and BAT metabolism

Chapman,

Brunet,

Mourier

et al. 2024

Preprint

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Mitochondria perform several essential functions in order to maintain cellular homeostasis and mitochondrial metabolism is inherently flexible to allow correct function in a wide range of tissues. Dysregulated mitochondrial metabolism can therefore affect different tissues in different ways which presents experimental challenges in understanding the pathology of mitochondrial diseases. System-level metabolic modelling is therefore useful in gaining in-depth insights into tissue-specific mitochondrial metabolism, yet despite the mouse being a common model organism used in research, there is currently no mouse specific mitochondrial metabolic model available. In this work, building upon the similarity between human and mouse mitochondrial metabolism, we have created mitoMammal, a genome-scale metabolic model that contains human and mouse specific gene-product reaction rules. MitoMammal is therefore able to model mouse and human mitochondrial metabolism. To demonstrate this feature, using an adapted E-Flux2 algorithm, we first integrated proteomic data extracted from mitochondria of isolated mouse cardiomyocytes and mouse brown adipocyte tissue. We then integrated transcriptomic data from in vitro differentiated human brown adipose cells and modelled the context specific metabolism using flux balance analysis. In all three simulations, mitoMammal made mostly accurate, and some novel predictions relating to energy metabolism in the context of cardiomyocytes and brown adipocytes. This demonstrates its usefulness in research relating to cardiac disease and diabetes in both mouse and human contexts.

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On paradoxes between optimal growth, metabolic control analysis, and flux balance analysis

Cited by 2 publications

References 83 publications

50 years of Metabolic Control Analysis: Its past and current influence in the biological sciences

50 years of Metabolic Control Analysis: Its past and current influence in the biological sciences

MitoMAMMAL: a genome scale model of mammalian mitochondria predicts cardiac and BAT metabolism

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