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Deletion of the mitochondrial carrier genes MRS3 and MRS4 suppresses mitochondrial iron accumulation in a yeast frataxin-deficient strain

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Foury, Françoise [UCL] Roganti, T.

The mitochondrial solute carriers Mrs3p and Mrs4p were originally isolated as multicopy suppressors of intron splicing defects. We show here that MRS4 is coregulated with the iron regulon genes, and up-regulated in a strain deficient for Yfh1p, the yeast homologue of human frataxin. Using in vivo Fe-55 cell radiolabeling we show that in glucose-grown cells mitochondrial iron accumulation is 5-15 times higher in DeltaYFH1 than in wildtype strain. However, although in a DeltaYFH1DeltaMRS3DeltaMRS4 strain, the intracellular Fe-55 content is extremely high, the mitochondrial iron concentration is decreased to almost wild-type levels. Moreover, DeltaYFH1DeltaMRS3DeltaMRS4 cells grown in high iron media do not lose their mitochondrial genome. Conversely, a DeltaYFH1 strain overexpressing MRS4 has an increased mitochondrial iron content and no mitochondrial genome. Therefore, MRS4 is required for mitochondrial iron accumulation in AYFH1 cells. Expression of the iron regulon and intracellular Fe-55 content are higher in a DeltaMRS3DeltaMRS4 strain than in the wild type. Nevertheless, the mitochondrial Fe-55 content, a balance between iron uptake and exit, is decreased by a factor of two. Moreover, Fe-55 incorporation into heme by ferrochelatase is increased in an MRS4-overexpressing strain. The function of MRS4 in iron import into mitochondria is discussed.

Document type Article de périodique (Journal article) – Article de recherche
Access type Accès restreint
Publication date 2002
Language Anglais
Journal information "Journal of Biological Chemistry" - Vol. 277, no. 27, p. 24475-24483 (2002)
Peer reviewed yes
Publisher Amer Soc Biochemistry Molecular Biology Inc (Bethesda)
issn 0021-9258
e-issn 1083-351X
Publication status Publié
Affiliation UCL - AGRO/CABI - Département de chimie appliquée et des bio-industries
Links
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Bibliographic reference Foury, Françoise ; Roganti, T.. Deletion of the mitochondrial carrier genes MRS3 and MRS4 suppresses mitochondrial iron accumulation in a yeast frataxin-deficient strain. In: Journal of Biological Chemistry, Vol. 277, no. 27, p. 24475-24483 (2002)
Permanent URL http://hdl.handle.net/2078.1/41840