Mathematical modelling of arsenic transport, distribution and detoxification processes in yeast.
Journal article, 2014

Arsenic has a dual role as causative and curative agent of human disease. Therefore, there is considerable interest in elucidating arsenic toxicity and detoxification mechanisms. By an ensemble modelling approach, we identified a best parsimonious mathematical model which recapitulates and predicts intracellular arsenic dynamics for different conditions and mutants, thereby providing novel insights into arsenic toxicity and detoxification mechanisms in yeast, which could partly be confirmed experimentally by dedicated experiments. Specifically, our analyses suggest that: (i) arsenic is mainly protein-bound during short-term (acute) exposure, whereas glutathione-conjugated arsenic dominates during long-term (chronic) exposure, (ii) arsenic is not stably retained, but can leave the vacuole via an export mechanism, and (iii) Fps1 is controlled by Hog1-dependent and Hog1-independent mechanisms during arsenite stress. Our results challenge glutathione depletion as a key mechanism for arsenic toxicity and instead suggest that (iv) increased glutathione biosynthesis protects the proteome against the damaging effects of arsenic and that (v) widespread protein inactivation contributes to the toxicity of this metalloid. Our work in yeast may prove useful to elucidate similar mechanisms in higher eukaryotes and have implications for the use of arsenic in medical therapy.



Molecular microbiology


Soheil Rastgou Talemi

Otto von Guericke Universitaet Magdeburg

Therese Jacobson

University of Gothenburg

Vijay Garla

Yale University

Clara Navarrete Roman

University of Gothenburg

Annemarie Wagner

Chalmers, Applied Physics

Markus J. Tamás

University of Gothenburg

J. Schaber

Otto von Guericke Universitaet Magdeburg

Molecular Microbiology

0950-382X (ISSN) 1365-2958 (eISSN)

Vol. 92 6 1343-56

Subject Categories

Biochemistry and Molecular Biology


Bioinformatics and Systems Biology





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