Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.9.3.1 (cytochrome oxidase)
 8,822 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An efficient handling of superoxides by antioxidant defenses is a crucial issue for cells with respiratory chain deficient mitochondria. We used human cultured skin fibroblasts to delineate the mechanism controlling the expression of antioxidant defenses in the case of a severe ATPase deficiency resulting from an 8993T>G mutation in the mitochondrial ATPase6 gene. We observed the nuclear translocation of the transcription factor Nrf2 associated with thinning of the actin stress fibers. The mobilization of the Nrf2 signaling pathway could be mimicked by a chemical blockade of the ATPase with a specific inhibitor, oligomycin. Interestingly enough, Nrf2 nuclear translocation was not observed in the case of a severe cytochrome oxidase deficiency, indicating that studying the status of this signaling pathway could throw some light on the importance of the oxidative insult associated with different respiratory chain defects.
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PMID:The mtDNA NARP mutation activates the actin-Nrf2 signaling of antioxidant defenses. 1826 63

Premature ovarian insufficiency (POI) is defined as the cessation of ovarian function under the age of 40 years and is characterized by amenorrhea, hypoestrogenism, and elevated serum gonadotrophin concentration (FSH). It is a heterogeneous disorder with a multicausal pathogenesis; however, majority of cases are idiopathic. In idiopathic POI, involvement of unknown mechanisms may increase rate of oocyte apoptosis. Studies have shown that elevated reactive oxygen species (ROS) levels affect the quality of gametes. Mitochondrial mutations in different complexes of electron transport chain have been reported to disrupt the electron flow which lead to formation of more superoxide ions or increased levels of ROS. This study was aimed to screen the mitochondrial genome for variations in idiopathic POI (n = 25) and occult ovarian insufficiency (OI) (n = 5) patients. 30 patients diagnosed with POI and occult OI were enrolled in this study. Blood samples were collected from the patients and controls. DNA was extracted using phenol chloroform method. A total of 102 nucleotide variations were observed in patients as compared with 58 nucleotide variations in controls. 24% variations were found to be non-synonymous and 76% were synonymous. It was found that 48% variations were in complex I, 8% in complex III, 24% in complex IV, and 20% in complex V of electron transport chain. We found most of the non-synonymous mitochondrial variations in complex I (48%) of the respiratory chain which is the largest enzyme complex and is associated with oxidative stress. Some non-synonymous pathogenic alterations (p.M31T, p.W239C, p.L128Q) and non pathogenic alterations (ATPase6:p.T53I, ATPase6:p.L190F, ATPase6:p.L199L) were found to be significantly higher in cases as compared with controls. The preliminary data suggest that the mitochondrial mutations and subsequent decline in ATP levels may accelerate follicular atresia and lead to POI. The results of this preliminary study highlight the need to extend this study by analyzing large number of samples in different ethnic populations and analyze for ROS levels and mitochondrial mutations in oocytes as they are of different embryonic origin and develop in a different microenvironment.
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PMID:Nucleotide variations in mitochondrial DNA and supra-physiological ROS levels in cytogenetically normal cases of premature ovarian insufficiency. 2068 Mar 10

This study investigated the genetic and enzymological features of Leigh syndrome due to respiratory chain complex deficiency in Chinese patients. The clinical features of 75 patients were recorded. Mitochondrial respiratory chain enzyme activities were determined via spectrophotometry. Mitochondrial gene sequence analysis was performed in 23 patients. Five core pedigrees were investigated via restriction fragment length polymorphism and gene sequencing. Psychomotor retardation (55%), motor regression (20%), weakness (29%), and epilepsy (25%) were the most frequent manifestations. Sixty-four patients (85.3%) had isolated respiratory complex deficiencies: complex I was seen in 28 patients (37.3%); complex II, seven (9.3%); complex III, six (8%); complex IV, ten (13.3%); and complex V, 13 patients (17.3%). Eleven patients (14.7%) had combined complex deficiencies. Mitochondrial DNA mutations were detected in 10 patients. Eight point mutations were found in mitochondrial structural genes: m.4833A>G in ND2, m.10191T>C in ND3, m.12338T>C and m.13513G>A in ND5, m.14502T>C and m.14487T>C in ND6, m.8108A>G in COXII, and m.8993T>G in ATPase6. Three mutations were found in tRNA genes: m.4395A>G in tRNA-Gln, m.10454T>C in tRNA-Arg, and m.5587T>C in tRNA-Ala. One patient and their mother both had the m.12338T>C and m.8993T>C mutations. In conclusion, mitochondrial respiratory chain complex I deficiency and structural gene mutations frequently occur in Chinese Leigh syndrome patients.
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PMID:Genetic and biochemical findings in Chinese children with Leigh syndrome. 2395 30