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Mitochondrial Dysfunction and Chronic Inflammation in Polycystic Ovary Syndrome.
Dabravolski, SA, Nikiforov, NG, Eid, AH, Nedosugova, LV, Starodubova, AV, Popkova, TV, Bezsonov, EE, Orekhov, AN
International journal of molecular sciences. 2021;(8)
Abstract
Polycystic ovarian syndrome (PCOS) is the most common endocrine-metabolic disorder affecting a vast population worldwide; it is linked with anovulation, mitochondrial dysfunctions and hormonal disbalance. Mutations in mtDNA have been identified in PCOS patients and likely play an important role in PCOS aetiology and pathogenesis; however, their causative role in PCOS development requires further investigation. As a low-grade chronic inflammation disease, PCOS patients have permanently elevated levels of inflammatory markers (TNF-α, CRP, IL-6, IL-8, IL-18). In this review, we summarise recent data regarding the role of mtDNA mutations and mitochondrial malfunctions in PCOS pathogenesis. Furthermore, we discuss recent papers dedicated to the identification of novel biomarkers for early PCOS diagnosis. Finally, traditional and new mitochondria-targeted treatments are discussed. This review intends to emphasise the key role of oxidative stress and chronic inflammation in PCOS pathogenesis; however, the exact molecular mechanism is mostly unknown and requires further investigation.
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Mitochondrial DNA 10158T>C mutation in a patient with mitochondrial encephalomyopathy with lactic acidosis, and stroke-like episodes syndrome: A case-report and literature review (CARE-complaint).
Wang, S, Song, T, Wang, S
Medicine. 2020;(24):e20310
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Abstract
RATIONALE Mitochondrial encephalomyopathy with lactic acidosis and stroke- like episodes (MELAS) syndrome is caused by mitochondrial respiratory chain dysfunction and oxidative phosphorylation disorder. It is a rare clinical metabolic disease involved with multiple systems. PATIENT CONCERNS A 22-year-old patient presented with limb convulsion accompanied by loss of consciousness, headache, partial blindness, blurred vision, and so on. DIAGNOSES Brain magnetic resonance imaging showed a high-intensity area in bilateral occipital cortex, left parietal lobe and cerebellum on diffusion-weighted imaging. These focus did not distribute as vascular territory. The pathological examination of skeletal muscle revealed several succinate dehydrogenase reactive vessels with overreaction and increased content of lipid droplets in some muscle fibers. Genetic testing showed that the patient carried m.10158T>C mutation. INTERVENTIONS She was provided with traditional arginine hydrochloride therapy and orally medication of coenzyme Q (10 mg). OUTCOMES Mitochondrial DNA of blood and hair follicle of patient carried m.10158T>C mutation LESSONS For the suspected patients of MELAS syndrome, if the hot-spot mutation test is negative, more detection sites should be selected.
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[SUCLA2-related encephalomyopathic mitochondrial DNA depletion syndrome: a case report and review of literature].
Liu, Z, Fang, F, Ding, C, Wu, H, Lyu, J, Wu, Y
Zhonghua er ke za zhi = Chinese journal of pediatrics. 2014;(11):817-21
Abstract
OBJECTIVE To analyze the clinical characteristics of SUCLA2-related encephalomyopathic mitochondrial DNA depletion syndrome (MDS) in one patient, and review the latest clinical research reports. METHOD Clinical, laboratory and genetic data of one case of SUCLA2-related encephalomyopathic MDS diagnosed by department of Neurology, Beijing Children's Hospital in November, 2013 were reported, and through taking "SUCLA2" as key words to search at CNKI, Wanfang, PubMed and the Human Gene Mutation Database (HGMD) professional to date, the clinical characteristics of 24 reported cases of SUCLA2-related encephalomyopathic MDS in international literature in combination with our case were analyzed. RESULT (1) The patient was 5 years and 9 months old, born as a term small for gestational age infant whose birth weight was 2 400 g, and presented since birth with severe muscular hypotonia, feeding difficulties, failure to thrive, psychomotor retardation and hearing impairment. Until now, he still showed severe developmental retardation, together with muscular atrophy, thoracocyllosis and scoliosis, and facial features. The patient is the first born from consanguineous healthy parents, whose relationship is cousins. Laboratory tests showed urinary excretion of mild methylmalonic acid (MMA), elevated plasma lactate concentration, and increased C3-carnitine and C4-dicarboxylic-carnitine in plasma carnitine ester profiling. MRI showed brain atrophy-like and bilateral T2 hyperintensities in bilateral caudate nuclei and putamen. By Next-Generation Sequencing (NGS), we identified a novel homozygous missense mutation (c.970G > A) in the SUCLA2 in a highly conserved amino acid residue. (2) The total number was only 25 with a male to female ratio of 14: 11, and age of onset of 23 was 0-4 months. The most common clinical features in patients with SUCLA2 mutation were permanent hypotonia, muscle atrophy, psychomotor retardation and scoliosis or kyphosis. Frequent signs included hearing impairment, hyperkinesia, dystonia or athetoid movements, feeding difficulties, growth retardation and ptosis or ophthalmoplegia. Epilepsy was occasionally observed. The combination of lactic acidemia, mild MMA-uria and increased C3-carnitine and C4-dicarboxylic-carnitine in plasma carnitine ester profiling were characteristic markers. MRI showed brain atrophy-like and bilateral basal ganglia involvement (mainly the putamen and caudate nuclei). Nineteen patients originated from Europe, with 13 of whom originated from Faroe Islands that carry a homozygous mutation (c.534+1G>A) in SUCLA2. CONCLUSION SUCLA2-related encephalomyopathic MDS is characterized by onset of severe hypotonia in early infancy, feeding difficulties, growth retardation, psychomotor retardation and hearing impairment. Metabolic findings usually include lactic acidemia, mild MMA-uria and increased C3-carnitine and C4-dicarboxylic-carnitine in plasma carnitine ester profiling. MRI showed brain atrophy-like and bilateral basal ganglia involvement (mainly the putamen and caudate nuclei). SUCLA2 pathogenic mutations would confirm the diagnosis.
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Mitochondrial diabetes and deafness: possible dysfunction of strial marginal cells of the inner ear.
Olmos, PR, Borzone, GR, Olmos, JP, Diez, A, Santos, JL, Serrano, V, Cataldo, LR, Anabalón, JL, Correa, CH
Journal of otolaryngology - head & neck surgery = Le Journal d'oto-rhino-laryngologie et de chirurgie cervico-faciale. 2011;(2):93-103
Abstract
OBJECTIVE Some patients with the syndrome of mitochondrial diabetes and deafness (MIDD) have a m.3243A>G mutation of the MTTL1 gene encoding transfer ribonucleic acid for the amino acid leucine (tRNALeu(UUR)). One of our MIDD patients inspired us to propose an integrated view on how a single mutation of the mitochondrial deoxyribonucleic acid (DNA) affects both the glucose metabolism and the inner ear physiology. DESIGN (a) Study of mitochondrial DNA in a patient with MIDD. (b) REVIEW OF THE LITERATURE on the impact of the m.3243A>G mutation on glucose metabolism and on the physiology of the hearing process. SETTINGS Outpatient diabetes and nutrition department and molecular nutrition laboratory. METHODS (a) Polymerase chain reaction followed by restriction fragment analysis identified the m.3243A>G mutation. (b) REVIEW OF THE LITERATURE from 1994 to 2009. RESULTS (a) Molecular study: the m.3243A>G mutation was detected with an appreciable level of heteroplasmy. (b) REVIEW OF THE LITERATURE the strial marginal cells located near the organ of Corti fulfill two characteristics: they are rich in mitochondria, and their dysfunction may produce neurosensorial deafness by means of a reduction in the potassium ion concentration of the endolymph. CONCLUSIONS The m.3243A>G mutation not only underlies a dysfunction of the insulin-producing beta cell of the pancreas but also results in a reduction in adenosine triphosphate production of the strial marginal cells of the inner ear, thus diminishing the energy (in the form of potassium ion gradient) needed for the outer hair cells of the organ of Corti to amplify the soundwaves, particularly at high frequencies.
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Mitochondrial haplogroups associated with lifestyle-related diseases and longevity in the Japanese population.
Nishigaki, Y, Fuku, N, Tanaka, M
Geriatrics & gerontology international. 2010;:S221-35
Abstract
Recently published results on the association between metabolic syndrome, type 2 diabetes, myocardial infarction or atherothrombotic cerebral infarction and Japanese major haplogroups based on the comprehensive analysis of mitochondrial genome polymorphisms (mtSNP) in the coding region of human mitochondrial DNA (mtDNA), and longevity-related haplogroups are described in the present review. Our aim was to provide information that would allow us to predict the genetic risk for lifestyle-related diseases and thereby contribute to the primary prevention of these conditions. The mitochondrial genome variation is so large that a given haplogroup might consist of various subhaplogroups carrying unique and presumably functional mtSNP. The frequency of each subhaplogroup is sometimes only a few percent. Therefore, large-scale association study is necessary for elucidating the impact of each subhaplogroup on the susceptibility to various common diseases.
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[Relationship between mitochondrial DNA and myelodysplastic syndromes - review].
Zhang, QQ, Li, X
Zhongguo shi yan xue ye xue za zhi. 2008;(3):712-6
Abstract
Mitochondria is the main place of biological oxidation and energy transform. Mitochondrial DNA encodes the complex of respiratory chain in mitochondria and its mutation can cause a series of human disease. Mitochondrial DNA mutation which observed in myelodysplastic syndrome (MDS) patients cause the MDS by the mechanism of iron metabolism disorder, gene instability and hemopoietic progenitor cell apoptosis. In this review the characteristics of mitochondrial DNA structure, the mitochondrial DNA mutation and the possible mechanism of mitochondrial DNA mutation in pathogenesis of MDS were summarized.
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From sideroblastic anemia to the role of mitochondrial DNA mutations in myelodysplastic syndromes.
Gattermann, N
Leukemia research. 2000;(2):141-51
Abstract
A primary mitochondrial defect may be pivotal in the pathogenesis of acquired idiopathic sideroblastic anemia (AISA). The mitochondrial respiratory chain is involved in mitochondrial iron uptake and supply of ferrous iron (Fe2+) for heme synthesis. Mitochondrial DNA (mtDNA) comes into play because several subunits of the respiratory chain are encoded by the mitochondrial genome. We have identified heteroplasmic mutations of mtDNA, which may not only impair mitochondrial iron metabolism and heme synthesis, but through impairment of mitochondrial energy production may have much broader implications for MDS pathogenesis. For example, increased apoptosis and genetic instability may be phenomena linked to mitochondrial dysfunction.