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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