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Article Dans Une Revue Biochemical Journal Année : 2006

GTP in the mitochondrial matrix plays a crucial role in organellar iron homoeostasis.

Résumé

Mitochondria are the major site of cellular iron utilization for the synthesis of essential cofactors such as iron-sulfur clusters and haem. In the present study, we provide evidence that GTP in the mitochondrial matrix is involved in organellar iron homoeostasis. A mutant of yeast Saccharomyces cerevisiae lacking the mitochondrial GTP/GDP carrier protein (Ggc1p) exhibits decreased levels of matrix GTP and increased levels of matrix GDP [Vozza, Blanco, Palmieri and Palmieri (2004) J. Biol. Chem. 279, 20850-20857]. This mutant (previously called yhm1) also manifests high cellular iron uptake and tremendous iron accumulation within mitochondria [Lesuisse, Lyver, Knight and Dancis (2004) Biochem. J. 378, 599-607]. The reason for these two very different phenotypic defects of the same yeast mutant has so far remained elusive. We show that in vivo targeting of a human nucleoside diphosphate kinase (Nm23-H4), which converts ATP into GTP, to the matrix of ggc1 mutants restores normal iron regulation. Thus the role of Ggc1p in iron metabolism is mediated by effects on GTP/GDP levels in the mitochondrial matrix.

Dates et versions

hal-00112642 , version 1 (09-11-2006)

Identifiants

Citer

Donna M Gordon, Elise R Lyver, Emmanuel Lesuisse, Andrew Dancis, Debkumar Pain. GTP in the mitochondrial matrix plays a crucial role in organellar iron homoeostasis.. Biochemical Journal, 2006, 400 (1), pp.163-8. ⟨10.1042/BJ20060904⟩. ⟨hal-00112642⟩
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