Titre :
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Increasing mitochondrial substrate-level phosphorylation can rescue respiratory growth of an ATP sunthase deficient yeast (abstract : congrès international de Myologie, 2005)
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contenu dans :
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Auteurs :
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Congrès international de myologie 2005 (International Congress of Myology 2005; 9-13 mai 2005; Nantes, France) ;
Schwimmer C ;
Lefebvre-Legendre L ;
Rak M ;
Devin A ;
Slonimski P ;
Di Rago JP ;
Rigoulet M
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Type de document :
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Article
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Année de publication :
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2005
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Pages :
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p. 184
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Langues:
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Anglais
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Mots-clés :
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chaîne respiratoire
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colloque
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corrélation génotype-phénotype
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degré de sévérité
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expression génique
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mécanisme d'action
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mitochondrie
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mutation génétique
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phosphorylation
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protéine mitochondriale
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synthèse d'ATP
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transport mitochondrial
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Résumé :
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Communication n° 693 In a previous study, we have identified Fmc1p, a mitochondrial protein involved in the assembly/stability of the yeast F0F1-ATP synthase at elevated temperature. The ?fmc1 mutant was shown to exhibit a severe phenotype of very slow growth on respiratory substrates at 37°C. We have isolated ODC1 as a multicopy suppressor of the fmc1 deletion restoring a good respiratory growth. Odc1p expression level was estimated to be at least 10 times higher in mitochondria isolated from the ?fmc1/ODC1 transformant as compared to wild type mitochondria. Interestingly, ODC1 encodes an oxodicarboxylate carrier, which transports alpha-ketoglutarate and alpha-ketoadipate or another transported TCA cycle intermediate in a counter-exchange through the inner mitochondrial membrane. We show that the suppression of the respiratory-growth deficient fmc1 by the over-expressed Odc1p was not due to a restored stable ATP synthase. Instead, the rescuing mechanism involves an increase in the flux of alpha-ketoglutarate from the cytosol into the mitochondria leading to an increase in the alpha-ketoglutarate oxidative decarboxylation resulting in an increase in mitochondrial substrate level dependent ATP synthesis. This mechanism of metabolic by-pass of a defective ATP synthase unravels the physiological importance of intra-mitochondrial substrate-level phosphorylations. This unexpected result might be of interest for the development of therapeutic solutions in pathologies associated with defects in the oxidative phosphorylation system.
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