Idioma:

Mathematical modelling of arsenic transport, distribution and detoxification processes in yeast

Talemi, Soheil Rastgou ; Jacobson, Therese ; Garla, Vijay ; Navarrete, Clara ; Wagner, Annemarie ; Tamás, Markus J. ; Schaber, Jörg

Molecular microbiology, 2014-06, Vol.92 (6), p.1343-1356 [Periódico revisado por pares]

England: Blackwell Publishing Ltd

Texto completo disponível

Citações Citado por

Enviar para

Título:
Mathematical modelling of arsenic transport, distribution and detoxification processes in yeast
Autor: Talemi, Soheil Rastgou ; Jacobson, Therese ; Garla, Vijay ; Navarrete, Clara ; Wagner, Annemarie ; Tamás, Markus J. ; Schaber, Jörg
Assuntos: Arsenic ; Arsenic - metabolism ; Biochemistry and Molecular Biology ; Bioinformatics and Systems Biology ; Bioinformatik och systembiologi ; Biokemi och molekylärbiologi ; Biotransformation ; Inactivation, Metabolic ; Mathematical models ; Microbiology ; Mikrobiologi ; Models, Theoretical ; Molecular biology ; Molecular microbiology ; Saccharomyces cerevisiae - metabolism ; Yeast
É parte de: Molecular microbiology, 2014-06, Vol.92 (6), p.1343-1356
Notas: ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
Descrição: Summary 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.
Editor: England: Blackwell Publishing Ltd
Idioma: Inglês

Links

Voltar para lista de resultados

Realização: Logos de Redes Sociais:

Mathematical modelling of arsenic transport, distribution and detoxification processes in yeast

Talemi, Soheil Rastgou ; Jacobson, Therese ; Garla, Vijay ; Navarrete, Clara ; Wagner, Annemarie ; Tamás, Markus J. ; Schaber, Jörg

England: Blackwell Publishing Ltd

Buscando em bases de dados remotas. Favor aguardar.