Mitochondria, Metals and Oxidative Stress

Group leader

By studying the assimilation pathways of iron and its intracellular metabolism in a model organism, the yeast Saccharomyces cerevisiae, we can address some of the fundamental problems of biology whilst considering new applications within the field of therapeutics or furthering our knowledge and understanding of the molecular bases of human pathologies.

Indeed, the question of the cellular and molecular mechanisms that are brought into play to control thecellular homeostasis of iron, an element that is essential for cellular metabolism but potentially toxic as a vector of oxidative stress, must be broached in terms of the analysisof complexsystems, which are very sensitive to variations in the parameters that control the responses to either a deficiency in or an excess of iron in the growth media and confer on cells an excellent capacity for adaptation. This adaptation can give rise to responses up to the supra-cellular level, as illustrated by the self-organization of yeast cells into colonies of differentiated morphology according to the bioavailability of iron in the growth medium (see photos)

We are using genetic and biochemical approaches to our studies, but we are also developing the important new methods now available in the field of genomics (DNA chips, Chromatin Immuno-precipitation, high density screening of collections of mutants, proteomic analyses, and measurement of molecular interactions).

Whilst studying the metabolism of iron in the model organism S. cerevisiae, we are also conducting similar work with another yeast, Candida albicans, putting emphasis in this case on the relationship between the metabolism of iron and pathogenicity. C. albicans, which is normally a human commensal, is known to be a major pathogen in hosts that are immunologically or physiologically compromised, and as such is responsible for a large number of nosocomial diseases that are often lethal.

Selection of Publications

Central role for ferritin in the day/night regulation of iron homeostasis in marine phytoplankton.
Botebol H, Lesuisse E, Šuták R, Six C, Lozano JC, Schatt P, Vergé V, Kirilovsky A, Morrissey J, Léger T, Camadro JM, Gueneugues A, Bowler C, Blain S, Bouget FY.
Proc Natl Acad Sci U S A. 2015 Nov 24;112(47):14652-7. Epub 2015 Nov 9.
Abstract

A novel protein, ubiquitous in marine phytoplankton, concentrates iron at the cell surface and facilitates uptake.
Morrissey J, Sutak R, Paz-Yepes J, Tanaka A, Moustafa A, Veluchamy A, Thomas Y, Botebol H, Bouget FY, McQuaid JB, Tirichine L, Allen AE, Lesuisse E, Bowler C.
Curr Biol. 2015 Feb 2;25(3):364-71. Epub 2014 Dec 31.
Abstract

The metacaspase (Mca1p) has a dual role in farnesol-induced apoptosis in Candida albicans.
Léger T, Garcia C, Ounissi M, Lelandais G, Camadro JM.
Mol Cell Proteomics. 2015 Jan;14(1):93-108. Epub 2014 Oct 27.
Abstract

Changes in glutathione-dependent redox status and mitochondrial energetic strategies are part of the adaptive response during the filamentation process in Candida albicans.
Guedouari H, Gergondey R, Bourdais A, Vanparis O, Bulteau AL, Camadro JM, Auchère F.
Biochim Biophys Acta. 2014 Sep;1842(9):1855-69. Epub 2014 Jul 10.
Abstract

bPeaks: a bioinformatics tool to detect transcription factor binding sites from ChIPseq data in yeasts and other organisms with small genomes.
Merhej J, Frigo A, Le Crom S, Camadro JM, Devaux F, Lelandais G.
Yeast. 2014 Oct;31(10):375-91. Epub 2014 Jul 28.
Abstract

The basis for evolution of DNA-binding specificity of the Aft1 transcription factor in yeasts.
Gonçalves IR, Conde e Silva N, Garay CL, Lesuisse E, Camadro JM, Blaiseau PL.
Genetics. 2014 Jan;196(1):149-60. Epub 2013 Oct 30.
Abstract

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