Mitochondria, Metals and Oxidative Stress
- Jean-Michel CAMADRO
Tel.: +33 (0)157278029
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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 the cellular 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 analysis of complex systems, 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.
Haemin-induced morphological change of C. albicans colonies.
(A) Colony of a wildtype strain (BWP17) grown with haemin as the sole iron source (YPD 1 mM BPS 50 mM haemin).
(B) Light microscope view of cells from the colony shown in (A).
(C) Colony of a wild-type strain (BWP17) grown in the presence of haemin (YPD 50 mM haemin).
(D) Colonies of the wild-type (1) and of mutant strains BWP17DCahmx1/CaHMX1 (2) and BWP17
DCahmx1/DCahmx1 (3) grown on YPD 25 mM haemin (upper view) or on YPD 75 mM haemin (lower view).
Selection of Publications
Apn1 AP-endonuclease is essential for the repair of oxidatively damaged DNA bases in yeast frataxin-deficient cells.
Lefevre S, Brossas C, Auchère F, Boggetto N, Camadro JM, Santos R.
Hum Mol Genet. 2012 Jun 16. [Epub ahead of print]
PubMed PMID: 22706278.
Changes in mitochondrial glutathione levels and protein thiol oxidation in ∆yfh1 yeast cells and the lymphoblasts of patients with Friedreich's ataxia.
Bulteau AL, Planamente S, Jornea L, Dur A, Lesuisse E, Camadro JM, Auchère F.
Biochim Biophys Acta. 2012 Feb;1822(2):212-25. Epub 2011 Nov 11.
Friedreich's ataxia: the vicious circle hypothesis revisited.
Bayot A, Santos R, Camadro JM, Rustin P.
BMC Med. 2011 Oct 11;9:112.
A Boolean probabilistic model of metabolic adaptation to oxygen in relation to iron homeostasis and oxidative stress.
Achcar F, Camadro JM, Mestivier D.
BMC Syst Biol. 2011 Apr 13;5:51.
Co-precipitation of phosphate and iron limits mitochondrial phosphate availability in Saccharomyces cerevisiae lacking the yeast frataxin homologue (YFH1).
Seguin A, Santos R, Pain D, Dancis A, Camadro JM, Lesuisse E.
J Biol Chem. 2011 Feb 25;286(8):6071-9. Epub 2010 Dec 28.
Dernière modification 7/01/2013