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)

Mitochondrial damage is often both the cause and outcome of cell injury resulting from a variety of toxic insults, hypoxia, or trauma. Increasing mitochondrial biogenesis after renal proximal tubular cell (RPTC) injury accelerated the recovery of mitochondrial and cellular functions (Biochem Biophys Res Commun 355:734-739, 2007). However, few pharmacological agents are known to increase mitochondrial biogenesis. We report that daidzein, genistein, biochanin A, formononetin, 3-(2',4'-dichlorophenyl)-7-hydroxy-4H-chromen-4-one (DCHC), 7-hydroxy-4H-chromen-4-one (7-C), 4'7-dimethoxyisoflavone (4',7-D), and 5,7,4'-trimethoxyisoflavone (5,7,4'-T) increased peroxisome proliferator-activated receptor gamma coactivator (PGC)-1alpha expression and resulted in mitochondrial biogenesis as indicated by increased expression of ATP synthase beta and ND6, and 1.5-fold increases in respiration and ATP in RPTC. Inhibition of estrogen receptors with ICI182780 (fulvestrant) had no effect on daidzein-induced mitochondrial biogenesis. The isoflavone derivatives showed differential effects on the activation and expression of sirtuin (SIRT)1, a deacetylase and activator of PGC-1alpha. Daidzein and formononetin induced the expression of SIRT1 in RPTC and the activation of recombinant SIRT1, whereas DCHC and 7-C only induced the activation of recombinant SIRT1. In contrast, genistein, biochanin A, 4',7-D, and 5,7,4'-T only increased SIRT1 expression in RPTC. We have identified a series of substituted isoflavones that produce mitochondrial biogenesis through PGC1alpha and increased SIRT1 activity and/or expression, independently of the estrogen receptor. Furthermore, different structural components are responsible for the activities of isoflavones: the hydroxyl group at position 7 is required SIRT1 activation, a hydroxyl group at position 5 blocks SIRT1 activation, and the loss of the phenyl ring at position 3 or the 4'-hydroxy or -methoxy substituent blocks increased SIRT1 expression.
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PMID:Isoflavones promote mitochondrial biogenesis. 1826 76

Leigh syndrome is a progressive neurodegenerative disorder occurring in infancy and childhood characterized in most cases by a psychomotor retardation, optic atrophy, ataxia, dystonia, failure to thrive, seizures and respiratory failure. In this study, we performed a systematic sequence analysis of mitochondrial genes associated with LS in Tunisian patients. We sequenced the encoded complex I units: ND2, ND3, ND4, ND5 and ND6 genes and the mitochondrial ATPase 6, tRNA(Val), tRNA(Leu(UUR)), tRNA(Trp) and tRNA(Lys) genes in 10 unrelated patients with Leigh syndrome. We revealed the presence of 34 reported polymorphisms, nine novel nucleotide variants and two new mutations (T5523G and A5559G) in the tested patients. These two mutations were localized in two conserved regions of the tRNA(Trp) and affect, respectively, the D-stem and the T-stem of the mitochondrial tRNA leading to a disruption of the secondary structure of this tRNA. SSP-PCR analysis showed that the T5523G and A5559G mutations were present with respective heteroplasmic rates of 66% and 43 %. We report here the first mutational screening of mitochondrial mutations in Tunisian patients with Leigh syndrome which described two novel mutations associated with this disorder.
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PMID:Two new mutations in the MT-TW gene leading to the disruption of the secondary structure of the tRNA(Trp) in patients with Leigh syndrome. 1934