Mitochondrial Dysfunction

Category: Writing
Date added
2019/04/18
Pages:  2
Words:  618
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Mitochondrial dysfunction in leukocytes from PCOS women with IR as compared to healthy controls was clearly evident by a decrease in mitochondrial oxygen (O2) consumption, oxidized gluthathione/glutathione ratio, significant increase in ROS production and decrease in MMP along with the defect in OXPHOS complex I activity. Hence, mitochondrial dysfunction may be a plausible link between IR and observed OS in these women [72]. Further PCOS women with IR showed impaired endothelium and mitochondrial dysfunction in leukocytes along with increase in inflammatory markers linked to IR suggesting that impaired OS and hampered leukocyte-endothelium interaction may be responsible for the increased risk of vascular disease in these women [73].

Gene expression profiles and global pathway analysis in skeletal muscle of PCOS women with IR and well-matched healthy control women revealed reduced expression of nuclear-encoded genes involved in mitochondrial oxidative metabolism and OXPHOS pathway as the most downregulated pathway [74]. Lee et al in 2011 first time found that mtDNA copy numbers in peripheral blood were significantly lower (P < .01) in PCOS women as compared to healthy controls irrespective of insulin indices and any other metabolic parameters and within PCOS group mtDNA copy number shows a negatively correlation with indices of IR, waist circumference, and triglyceride levels and positively correlation with sex hormone-binding globulin levels [75]. A recent study shows that adolescent non obese women with PCOS have peripheral IR which relates to muscle mitochondrial dysfunction during exercise. The ADP time constant and PCr time constant, representative of the rates of recovery of PCr and ADP depletion after exercise, were lower in PCOS women than in normal controls.

However, the study had some limitations such as small sample size and age range of women being 12 to 19 years hence differential effects of the growth hormone axis cannot be excluded [76]. Comparison of mitochondrial contribution to obesity-induced insulin resistance compared with lean, insulin-sensitive women with PCOS revealed aberrant skeletal muscle mitochondrial physiology. Obese PCOS women with IR exhibited lower mitochondrial phosphorylation efficiency and increased mitochondrial H2O2 emissions as compared to lean insulin-sensitive PCOS women. However, maximal whole-body and mitochondrial O2 consumption were not found to be different between obese and lean women. Twelve weeks of aerobic exercise training in obese PCOS women with IR restores mitochondrial physiology toward that of lean, insulin-sensitive individuals and also reversed obesity-related mitochondrial impairments indicating improved cellular redox status as a potential mechanism leading to improved insulin sensitivity (Konopka et al 2015).

Analysis of mitochondrial apoptotic pathway in cumulus cells surrounding mature oocytes revealed significantly higher BCL2 mRNA expression and no variation in BAX mRNA concentrations than those associated with immature oocytes of PCOS women. Even BCL2 mRNA content found in cumulus cells enclosing fertilized oocytes was higher. Hence, BCL2 expression is strongly associated with the ability of oocytes to compete nuclear maturation and to be fertilized (Filali et al., 2009). A study by Zhao et al in 2015 highlight that a cross talk between altered metabolic signals in the follicular niche and dysfunctional mitochondria in the cumulus cells of PCOS women may be involved in the pathogenesis of PCOS (Zhao et al., 2015).

Zhao and group performed targeted metabolomics study of follicular fluid of PCOS women and showed altered metabolic pathways such as upregulated glycolysis pathway, upregulated TCA cycle, upregulated BCAA catabolism pathway with increased Fatty acid ?-oxidation and decreased NAD catabolism and mitochondrial dysfunction (abnormal mitochondrial structures, decreased MMP, decreased perinuclear mitochondrial distribution, decreased mitochondrial biogenesis, and dysregulated mitophagy) in cumulus cells. Thus, follicular micro environment may induce mitochondrial dysfunction in cumulus cells possibly by epigenetic mechanism and vice versa. Recently, impaired glycolysis and increased mitochondrial activity and mitochondria-dependent apoptosis was shown in PCOS women with endometrial hyperplasia, an early hallmark of endometrial cancer suggesting mitochondrial pathways in inducing endometrial cancer in PCOS women.

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Mitochondrial dysfunction. (2019, Apr 18). Retrieved from https://papersowl.com/examples/mitochondrial-dysfunction/

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