Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0016719 (Friedreich's ataxia)
 2,098 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The activity of 7 mitochondrial enzymes, fumarase, NAD-malate dehydrogenase (MDH), citrate synthase (CS), valine dehydrogenase (VDH), succinate dehydrogenase (SDH), glutamate dehydrogenase (GDH), pyruvate dehydrogenase complex (PDHC) has been measured in platelet preparations from patients affected by Friedreich's ataxia (FA), dominant and non-dominant olivopontocerebellar atrophy (DOPCA, NDOPCA) and normal individuals. Significant decreases of GDH (P less than 0.01), PDHC (P less than 0.01), VDH (P less than 0.05) and SDH (P less than 0.05) activities were observed in FA patients. Significant decreases of GDH (P less than 0.01), PDHC (P less than 0.01), VDH (P less than 0.05), SDH (P less than 0.05) and CS (P less than 0.05) activities were Observed in ND-OPCA patients, whereas in DOPCA patients only GDH activity was significantly (P less than 0.05) decreased. In 8 of 10 patients with FA and in all patients with NDOPCA the activity of one or more of 4 enzymes, i.e. GDH, VDH, SDH, PDHC, was lower than the lowest of control values. Four of 6 patients with DOPCA had GDH activity lower than the lowest of control values. These results indicate that abnormalities of mitochondrial metabolism is a constant element in hereditary ataxia and suggest that the alteration primary leading to the different types of ataxias should be related to mitochondrial oxidative metabolism, at least at a regulatory level.
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PMID:Abnormalities of mitochondrial enzymes in hereditary ataxias. 281 70

Frataxin is a small conserved mitochondrial protein; in humans, mutations affecting frataxin expression or function result in Friedreich's ataxia. Much of the current understanding of frataxin function comes from informative studies with yeast models, but considerable debates remain with regard to the primary functions of this ubiquitous protein. We exploit the tractable reverse genetics of Trypanosoma brucei in order to specifically consider the importance of frataxin in an early branching lineage. Using inducible RNAi, we show that frataxin is essential in T. brucei and that its loss results in reduced activity of the marker Fe-S cluster-containing enzyme aconitase in both the mitochondrion and cytosol. Activities of mitochondrial succinate dehydrogenase and fumarase also decreased, but the concentration of reactive oxygen species increased. Trypanosomes lacking frataxin also exhibited a low mitochondrial membrane potential and reduced oxygen consumption. Crucially, however, iron did not accumulate in frataxin-depleted mitochondria, and as T. brucei frataxin does not form large complexes, it suggests that it plays no role in iron storage. Interestingly, RNAi phenotypes were ameliorated by expression of frataxin homologues from hydrogenosomes of another divergent protist Trichomonas vaginalis. Collectively, the data suggest trypanosome frataxin functions primarily only in Fe-S cluster biogenesis and protection from reactive oxygen species.
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PMID:Ancestral roles of eukaryotic frataxin: mitochondrial frataxin function and heterologous expression of hydrogenosomal Trichomonas homologues in trypanosomes. 1843 47