Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.6.3.14 (ATP synthase)
 7,042 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Finland and the Finns have been the subject of numerous genetic and genealogical studies, owing to enrichment of certain rare hereditary disorders in the Finnish population. Two types of NCL have so-far been found almost exclusively in Finland: Finnish variant late infantile NCL, vLINCL (CLN5), and the Northern epilepsy syndrome or Progressive epilepsy with mental retardation, EPMR (CLN8). The first symptoms of Finnish vLINCL are concentration problems or motor clumsiness by 3 to 6 years of age, followed by mental retardation, visual failure, ataxia, myoclonus, and epilepsy. Northern epilepsy, the newest member of the NCL family with the most protracted course, is characterized by the onset of generalized seizures between 5 and 10 years of age and subsequent progressive mental retardation. Visual problems are slight and late, while myoclonus has not been observed. Both the Finnish vLINCL and Northern epilepsy are pathologically characterized by intraneuronal cytoplasmic deposits of autofluorescent granules which are Luxol fast blue-, PAS-, and Sudan black B-positive in paraffin sections. In Northern epilepsy the intraneuronal storage process and neuronal destruction are generally of mild degree but highly selective and, in contrast to other forms of childhood onset NCL, the cerebellar cortex is relatively spared. By electron microscopy the storage bodies mainly contain rectilinear complex type and fingerprint profiles in Finnish vLINCL and structures resembling curvilinear profiles in Northern epilepsy. Mitochondrial ATP synthase subunit c is the main stored protein in both disorders. Both the DCLN5 and CLN8 genes encode putative membrane proteins with yet unknown functions. Furthermore, a well studied spontaneously occurring autosomal recessive mouse mutant, motor neuron degeneration (mnd) mouse, is a homolog for CLN8.
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PMID:Studies of homogenous populations: CLN5 and CLN8. 1133 69

PAS kinase 1 (Psk1) is a key regulator of respiration in Saccharomyces cerevisiae Herein the molecular mechanisms of this regulation are explored through the characterization of its substrate, Centromere binding factor 1 (Cbf1). CBF1-deficient yeast displayed a significant decrease in cellular respiration, while PAS kinase-deficient yeast, or yeast harboring a Cbf1 phosphosite mutant (T211A) displayed a significant increase. Transmission electron micrographs showed an increased number of mitochondria in PAS kinase-deficient yeast consistent with the increase in respiration. Although the CBF1-deficient yeast did not appear to have an altered number of mitochondria, a mitochondrial proteomics study revealed significant differences in the mitochondrial composition of CBF1-deficient yeast including altered Atp3 levels, a subunit of the mitochondrial F1-ATP synthase complex. Both beta-galactosidase reporter assays and western blot analysis confirmed direct transcriptional control of ATP3 by Cbf1 In addition, we confirmed the regulation of yeast lipid genes LAC1 and LAG1 by Cbf1 The human homolog of Cbf1, Upstream transcription factor 1 (USF1), is also known to be involved in lipid biogenesis. Herein, we provide the first evidence for a role of USF1 in respiration since it appeared to complement Cbf1 in vivo as determined by respiration phenotypes. In addition, we confirmed USF1 as a substrate of human PAS kinase (hPASK) in vitro Combined, our data supports a model in which Cbf1/USF1 functions to partition glucose toward respiration and away from lipid biogenesis, while PAS kinase inhibits respiration in part through the inhibition of Cbf1/USF1.
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PMID:The Regulation of Cbf1 by PAS Kinase Is a Pivotal Control Point for Lipogenesis vs. Respiration in Saccharomyces cerevisiae. 3038 Dec 92