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M Tondo,
F Ramon,
I Málaga,
M O'Callaghan,
M Serrano,
S Emperador,
A Ormazabal, E Ruiz-Pesini,
J Montoya,
M T Garcia-Silva,
A Garcia-Cazorla,
M Pineda,
R Artuch
Clinical biochemistry 05/2011; 44(7):546. · 2.02 Impact Factor
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ABSTRACT: Neurogenic muscle weakness, ataxia and retinitis pigmentosa (NARP) syndrome have been associated to m.8993T>G/C mutations in the subunit 6 of the ATP synthase (p.MT-ATP6).
We have performed a mutational screening of the mitochondrial DNA gene encoding for this protein in 62 patients with the disease, that do not carry any of the common mutations described to date.
We report clinical and molecular data in one patient who harbours a de novo insertion in the MT-ATP6 gene that results in a truncated subunit. The mutation was heteroplasmic (85%) in muscle DNA and the BN-PAGE analysis showed a clear decrease in the amount of ATP synthase.
Molecular analysis of NARP patients cannot be limited to the search of the m.8993T>G/C and either the ATP6 or the whole mtDNA should be sequenced.
Journal of Medical Genetics 01/2009; 46(1):64-7. · 6.36 Impact Factor
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ABSTRACT: Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is caused by mutations in the thymidine phosphorylase gene (ECGF1). We present the first detailed report of a Brazilian MNGIE patient, harboring a novel ECGF1 homozygous mutation (C4202A, leading to a premature stop codon, S471X). Multiple deletions and the T5814C change were found in mitochondrial DNA. Together with gastrointestinal symptoms, endocrine involvement and memory dysfunction, not reported in MNGIE to date, were the most preeminent features.
European Journal of Neurology 06/2007; 14(5):581-5. · 3.69 Impact Factor
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ABSTRACT: Cellular parameters of the seminogram have been previously shown to correlate with L-carnitine concentration in the seminal fluid. Carnitine is involved in a variety of metabolic processes playing an important role in maintaining an active oxidative phosphorylation (OXPHOS). Recently, we have found a significant association between the specific activities of the respiratory chain complexes and the seminogram parameters and here we have studied the relationship between the spermatozoa OXPHOS activities and L-carnitine concentration in the seminal plasma. Carnitine, but not prostatic secretions, positive and significantly correlate with mitochondrial respiratory complex activities and the citric acid cycle enzymes citrate synthase and succinate dehydrogenase. It is remarkable that the ratios of the respiratory chain complexes to citrate synthase or succinate dehydrogenase, significant but negatively correlated with L-carnitine concentration. As carnitine in seminal plasma is secreted from the epididymis our results strongly suggest that relationships between carnitine secretion, seminal quality and OXPHOS activities could be because of a parallel response to the same regulatory event.
International Journal of Andrology 01/2002; 24(6):335-40. · 3.59 Impact Factor
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ABSTRACT: Oligozoospermia is an important manifestation of male subfertility and very little attention has been paid to study a possible relationship between the total number of ejaculated spermatozoa and mitochondrial functionality. In this work we report a direct correlation between spectrophotometrically measured mitochondrial enzyme activities (citrate synthase and respiratory complex I, II, I+III, II+III and IV) and seminogram parameters (sperm motility, vitality and cell concentration). In addition, total ejaculated spermatozoa correlate much better with the nuclear-encoded citrate synthase and complex II than with the mitochondrial-encoded complex I, III and IV activities. Furthermore, total number of spermatozoa has a significant but negative correlation with the ratios of complex I, complex III and complex IV to complex II (and citrate synthase). These ratios are significantly higher in aged subjects emphasizing the physiological relevance of this observation. These results suggest that the simultaneous increase of the number of ejaculated spermatozoa and the mitochondrial enrichment of citrate synthase and complex II are both parallel responses to the same regulatory events.
Clinica Chimica Acta 11/2000; 300(1-2):97-105. · 2.54 Impact Factor
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E Ruiz-Pesini,
A C Lapeña,
C Díez-Sánchez,
A Pérez-Martos,
J Montoya,
E Alvarez,
M Díaz,
A Urriés,
L Montoro,
M J López-Pérez,
J A Enríquez
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ABSTRACT: A variety of mtDNA mutations responsible for human diseases have been associated with molecular defects in the OXPHOS system. It has been proposed that mtDNA genetic alterations can also be responsible for sperm dysfunction. In addition, it was suggested that if sperm dysfunction is the main phenotypic consequence, these mutations could be fixed as stable mtDNA variants, because mtDNA is maternally inherited. To test this possibility, we have performed an extensive analysis of the distribution of mtDNA haplogroups in white men having fertility problems. We have found that asthenozoospermia, but not oligozoospermia, is associated with mtDNA haplogroups in whites. Thus, haplogroups H and T are significantly more abundant in nonasthenozoospermic and asthenozoospermic populations, respectively, and show significant differences in their OXPHOS performance.
The American Journal of Human Genetics 10/2000; 67(3):682-96. · 10.60 Impact Factor
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ABSTRACT: Highly species-specific primers for pork D-loop mtDNA have been designed. Use of these and restrictive PCR amplification conditions has improved a reliable and rapid method for detecting a PCR-amplified 531 bp band from pork. It has been proved useful for detecting both pork meat and fat in meat mixtures, including those dry-cured and heated by cooking. Absence of response in PCR-amplified samples or mixtures from bovine, ovine, chicken, and human was also demonstrated. Furthermore, wild boar and pork samples can be also easily distinguished by a simple AvaII restriction analysis.
Journal of Agricultural and Food Chemistry 08/2000; 48(7):2829-32. · 2.82 Impact Factor
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J A Molina, E Ruiz-Pesini,
F J Jiménez-Jiménez,
M J López-Pérez,
E Alvarez,
A Berbel,
M Ortí-Pareja,
M Zurdo,
A Tallón-Barranco,
F de Bustos,
J Arenas
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ABSTRACT: We studied respiratory chain enzyme activities in spermatozoa homogenates from 12 untreated Parkinson's disease (PD) male patients and from 23 age matched healthy male controls. When compared with controls, PD patients showed significantly lower specific activities for complexes I+ III, II+III, and IV. However, citrate synthase corrected activities were similar in patients and controls. Values for enzyme activities in the PD group did not correlate with age at onset, duration, scores of the Unified Parkinson's Disease Rating Scales and Hoehn and Yahr staging. These results suggest that this tissue cannot be used to develop a diagnostic test for PD.
Acta Neurovegetativa 02/1999; 106(9-10):919-24. · 2.73 Impact Factor
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ABSTRACT: Until now, little attention has been paid to the contribution of mitochondrial dysfunction to germinal tissue disorders. The target of this study was to investigate the relationship between sperm motility and mitochondrial respiratory chain enzyme activities. The results obtained showed that semen samples of control individuals (n = 33) have substantially higher activities of complexes I, II, and IV compared with those of asthenozoospermic subjects (n = 86). Moreover, a direct and positive correlation was found in the whole population studied between spermatozoa motility and all the mitochondrial respiratory complex activities assayed (I, II, I+III, II+III, and IV). The ratio of these enzymes to citrate synthase (a reliable enzymatic marker of mitochondrial volume) activities did not correlate with sperm motility. This suggests that motility depends largely on the mitochondrial volume within the sperm midpiece. These observations could be of physiopathological relevance because they suggest that factors affecting the mitochondrial energy production could be then responsible for particular cases of idiopathic asthenozoospermia.
Clinical Chemistry 09/1998; 44(8 Pt 1):1616-20. · 7.91 Impact Factor
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ABSTRACT: Mitochondrial encephalopathy, lactic acidosis and cerebrovascular accident syndrome (MELAS) is, from the clinical point of view, one of the best studied mitochondrial multisystemic disorders. This disease has mainly been associated to the mitochondrial desoxyribonucleic acid (mtDNA) mutation A3243G located in the tRNALeu(UUR) gene. Although a relation between European haplogroups and the presence of the 3243 mutation has not been described, nothing is known about the presence of this mutation in native American haplogroups.
A 12 year-old female Mexican patient diagnosed with MELAS is reported. Besides neurological, biochemical and cytological examination, we also analyzed the particular mtDNA mutations related to MELAS and the whole genome was sequenced to determine the mitochondrial haplogroup. The A3243G mutation was detected in the patient and maternal relatives (mother and siblings, all of them asymptomatic). The genotype corresponds to the native American haplogroup B2 and contains two private non-synonymous polymorfisms.
All the members of the family studied present different percentage of the A3243G mutation, being the patient who presented the highest value. The mtDNA genotype corresponds to the native American haplogroup B2 and the private polymorphisms do not confer any phenotypic modification in MELAS syndrome.
Revista de neurologia 44(1):18-22. · 0.65 Impact Factor
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ABSTRACT: The diseases of the oxidative phosphorylation system consist of a group of disorders originated by a deficient synthesis of adenosine triphosphate (ATP). These diseases are increasingly being diagnosed among patients with multisystemic disorders. Mitochondrial deoxyribonucleic acid (mtDNA) mutations are usually maternally inherited, but they also can be sporadic or secondary to nuclear mutations, that are inherited in a Mendelian mode, or due to environmental hazards. In this review we will update, from a genetic point of view, the knowledge on human mitochondrial diseases, remarking the difficulties to study these pathologies.
To mirror these difficulties, we will use selected examples of mutations in the mitochondrial genome, and review recent advances on mitochondrial pathology due to mutations in the nuclear genes codifying for mitochondrial proteins that participate in a good performance of the oxidative phosphorylation system.
Sequencing of the complete human mtDNA should be part of the basic profile in the study of mitochondrial diseases. Due to the increasing number of nuclear genes involved in the oxidative phosphorylation system performance, their analysis should be based on solid biochemical clues.
Revista de neurologia 43(7):416-24. · 0.65 Impact Factor
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ABSTRACT: Leigh syndrome is a neurodegenerative and progressive disease that appears usually in childhood due to defects in nuclear or mitochondrial genome. The mutation G14459A in mitochondrial DNA has been associated previously to Leber hereditary optic neuropathy and recently to Leigh syndrome.
A 10 months-old Mexican girl diagnosed of Leigh syndrome. Molecular-genetic studies detected the mutation G14459A in a percentage close to homoplasmy and in low heteroplasmy in her mother. The rest of the maternally related family members analyzed were negative.
The G14459A mutation, although not very frequently associated to Leigh syndrome, should be analyzed in patients that do not present the most common point mutations.
Revista de neurologia 49(5):248-50. · 0.65 Impact Factor
