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Cited by 8Gene Regulatory Network AnalysisMicrobial Metabolic Engineering and BioproductionFungal and yeast genetics research

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A Boolean probabilistic model of metabolic adaptation to oxygen in relation to iron homeostasis and oxidative stress

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Achcar, Fiona, Camadro, Jean-Michel, Mestivier, Denis·2011·BMC Systems Biology
DOI 10.1186/1752-0509-5-51PMC PMC3094212
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Abstract

Background: In aerobically grown cells, iron homeostasis and oxidative stress are tightly linked processes implicated in a growing number of diseases. The deregulation of iron homeostasis due to gene defects or environmental stresses leads to a wide range of diseases with consequences for cellular metabolism that remain poorly understood. The modelling of iron homeostasis in relation to the main features of metabolism, energy production and oxidative stress may provide new clues to the ways in which changes in biological processes in a normal cell lead to disease. Results: Using a methodology based on probabilistic Boolean modelling, we constructed the first model of yeast iron homeostasis including oxygen-related reactions in the frame of central metabolism. The resulting model of 642 elements and 1007 reactions was validated by comparing simulations with a large body of experimental results (147 phenotypes and 11 metabolic flux experiments). We removed every gene, thus generating in silico mutants. The simulations of the different mutants gave rise to a remarkably accurate qualitative description of most of the experimental phenotype (overall consistency > 91.5%). A second validation involved analysing the anaerobiosis to aerobiosis transition. Therefore, we compared the simulations of our model with different levels of oxygen to experimental metabolic flux data. The simulations reproducted accurately ten out of the eleven metabolic fluxes. We show here that our probabilistic Boolean modelling strategy provides a useful description of the dynamics of a complex biological system. A clustering analysis of the simulations of all in silico mutations led to the identification of clear phenotypic profiles, thus providing new insights into some metabolic response to stress conditions. Finally, the model was also used to explore several new hypothesis in order to better understand some unexpected phenotypes in given mutants. Conclusions: All these results show that this model, and the underlying modelling strategy, are powerful tools for improving our understanding of complex biological problems.

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  • Neurodegenerative diseases such as PD, AD, amyotrophic lateral sclerosis, Huntington's disease, Friedreich's ataxia, and aceruloplasminemia have been linked to iron.

    “Neurodegenerative diseases such as PD, AD, amyotrophic lateral sclerosis, Huntington's disease, Friederich's ataxia and aceruloplasminemia have been linked to iron (Achcar et al., 2011)”

    From Iron, Oxidative Stress and Health (2012) · cites this paper as Achcar et al., 2011

    The Background (page unavailable) identifies Alzheimer’s and Parkinson’s diseases as neurodegenerative disorders, but links them to respiratory-chain or cellular-defence disruptions rather than specifically to iron. The passages found do not establish an iron link for either disease or address the other four named diseases. (LLM, conf=0.78)

    Experimental — accuracy not yet measured

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Metadata

Authors
Achcar, F., Camadro, J.-M., & Mestivier, D.
Affiliations
Centre National de la Recherche Scientifique (FR)
Corresponding author
Mestivier, Denis
ORCID
Venue
BMC Systems Biology
Publisher
Springer Science and Business Media LLC
Published
2011-04-13
Volume
5
Issue
1
Pages
51-51
ISSN
1752-0509 (ISSN-L)
DOI
10.1186/1752-0509-5-51
PMC
PMC3094212
OpenAlex
W2098919533
Cited by
8
References
4
Citations by year
2026: 1 · 2020: 1 · 2019: 1 · 2018: 1 · 2015: 1 · 2014: 1 · 2013: 1 · 2012: 1
FWCI
0.37
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • BMC Systems Biology (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam) (acceptedVersion)
  • HAL (submittedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gene Regulatory Network Analysis
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Microbial Metabolic Engineering and Bioproduction
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
Keywords
iron homeostasis, oxidative stress, oxygen metabolism, yeast metabolism, metabolic flux, central carbon metabolism, phenotypic profiles, metabolic adaptation
MeSH terms
Aerobiosis, Computer Simulation, Homeostasis, Iron, Models, Biological, Mutation, Oxygen, Phenotype, Saccharomyces cerevisiae, Oxidative Stress, Evolution, Molecular

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