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)

The mitochondrial changes in the ovary during the ovarian cycle are adapted to a cyclically increased-decreased energy demand. In the proliferative phase, the increased energy needs are sustained by the recruitment of mitochondria in active state 3, by an increased tissue O2 consumption and ATP production and by an increase in the number of mitochondria. In the phase of decreased energy needs, mitochondria-dependent apoptosis reduces tissue and mitochondrial O2 uptake. The ovary morphological changes during the cycle describe a process in which the follicles undergo a clear cycle with two sequential phases: proliferation and apoptosis. The follicular growth stimulated by FSH characterizes a tissue that shows a quick cell proliferation. During the ovarian cycle, tissue and mitochondrial O2 uptakes, mitochondrial mass, mitochondrial NO production and cytochrome oxidase activity exhibit a biphasic pattern, with marked increases in the ovary proliferative phases. Relatively low levels of NO seem to drive the cell signaling for follicle proliferation, whereas relatively high NO levels trigger mitochondria-dependent follicle apoptosis.
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PMID:Role of nitric oxide on mitochondrial biogenesis during the ovarian cycle. 1712 69

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