Mitochondrial coupling and capacity of oxidative phosphorylation in skeletal muscle of Inuit and Caucasians in the arctic winter.

During evolution, mitochondrial DNA haplogroups of arctic populations may have been selected for lower coupling of mitochondrial respiration to ATP production in favor of higher heat production. We show that mitochondrial coupling in skeletal muscle of traditional and westernized Inuit habituating northern Greenland is identical to Danes of western Europe haplogroups. Biochemical coupling efficiency was preserved across variations in diet, muscle fiber type, and uncoupling protein-3 content. Mitochondrial phenotype displayed plasticity in relation to lifestyle and environment. Untrained Inuit and Danes had identical capacities to oxidize fat substrate in arm muscle, which increased in Danes during the 42 days of acclimation to exercise, approaching the higher level of the Inuit hunters. A common pattern emerges of mitochondrial acclimatization and evolutionary adaptation in humans at high latitude and high altitude where economy of locomotion may be optimized by preservation of biochemical coupling efficiency at modest mitochondrial density, when submaximum performance is uncoupled from VO2max and maximum capacities of oxidative phosphorylation.

Modificación de la acción fisiológica de la FSH por las variantes genéticas de su receptor (FSHr) / No disponible

No disponible

Enfermedades del sistema de fosforilación oxidativa mitocondrial humano / Diseases of the human mitochondrial oxidative phosphorylation system

Objetivo. Las enfermedades del sistema de fosforilaciónoxidativa se originan por una deficiente producción de adenosíntrifosfato (ATP) por la mitocondria. Estas enfermedades se diagnosticanfrecuentemente entre pacientes con síntomas multisistémicosaparentemente no relacionados. Las mutaciones del ácidodesoxirribonucleico mitocondrial (ADNmt) pueden ser de herenciamaterna, esporádicas o producirse como consecuencia de mutacionesen genes nucleares que regulan la biosíntesis del ADNmt, y, portanto, con herencia mendeliana, o por causas ambientales. Estarevisión pretende actualizar, desde un punto de vista genético, elconocimiento sobre las enfermedades mitocondriales, a la vez quemostrar las dificultades que comporta el estudio de esta patología.Desarrollo. Para reflejar estas dificultades se utilizan ejemplos seleccionadosde mutaciones en el genoma mitocondrial asociadas adeterminadas enfermedades. También se revisan los avances recientessobre patología mitocondrial debida a mutaciones en genesnucleares, codificantes de proteínas mitocondriales que, directa oindirectamente, participan en el buen funcionamiento del sistemade fosforilación oxidativa. Conclusiones. La secuenciación completadel ADNmt, por su accesibilidad, debería ser parte del perfilbásico en el estudio de las enfermedades mitocondriales, pero dadala cantidad de genes nucleares que pueden afectar el sistema defosforilación oxidativa, su estudio debería estar sustentado en sólidosindicios bioquímicos

Aim. The diseases of the oxidative phosphorylation system consist of a group of disorders originated by a deficientsynthesis of adenosine triphosphate (ATP). These diseases are increasingly being diagnosed among patients with multisystemicdisorders. Mitochondrial deoxyribonucleic acid (mtDNA) mutations are usually maternally inherited, but they alsocan 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 thedifficulties to study these pathologies. Development. To mirror these difficulties, we will use selected examples of mutations inthe mitochondrial genome, and review recent advances on mitochondrial pathology due to mutations in the nuclear genescodifying for mitochondrial proteins that participate in a good performance of the oxidative phosphorylation system.Conclusions. Sequencing of the complete human mtDNA should be part of the basic profile in the study of mitochondrialdiseases. Due to the increasing number of nuclear genes involved in the oxidative phosphorylation system performance, theiranalysis should be based on solid biochemical clues

[Diseases of the human mitochondrial oxidative phosphorylation system]. / Enfermedades del sistema de fosforilación oxidativa mitocondrial humano.

AIM: 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. DEVELOPMENT: 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. CONCLUSIONS: 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.

Skeletal muscle mitochondrial DNA content in exercising humans.

Several weeks of intense endurance training enhances mitochondrial biogenesis in humans. Whether a single bout of exercise alters skeletal muscle mitochondrial DNA (mtDNA) content remains unexplored. Double-stranded mtDNA, estimated by slot-blot hybridization and real time PCR and expressed as mtDNA-to-nuclear DNA ratio (mtDNA/nDNA) was obtained from the vastus lateralis muscle of healthy human subjects to investigate whether skeletal muscle mtDNA changes during fatiguing and nonfatiguing prolonged moderate intensity [2.0-2.5 h; approximately 60% maximal oxygen consumption (Vo(2 max))] and short repeated high-intensity exercise (5-8 min; approximately 110% Vo(2 max)). In control resting and light exercise (2 h; approximately 25% Vo(2 max)) studies, mtDNA/nDNA did not change. Conversely, mtDNA/nDNA declined after prolonged fatiguing exercise (0.863 +/- 0.061 vs. 1.101 +/- 0.067 at baseline; n = 14; P = 0.005), remained lower after 24 h of recovery, and was restored after 1 wk. After nonfatiguing prolonged exercise, mtDNA/nDNA tended to decline (n = 10; P = 0.083) but was reduced after three repeated high-intensity exercise bouts (0.900 +/- 0.049 vs. 1.067 +/- 0.071 at baseline; n = 7; P = 0.013). Our findings indicate that prolonged and short repeated intense exercise can lead to significant reductions in human skeletal muscle mtDNA content, which might function as a signal stimulating mitochondrial biogenesis with exercise training.

Variabilidad del DNA mitocondrial (clados y dosis genómica) y calidad seminal humana / Epidemiology of hepatitis C in health care workers. Routes of transmission

Son muchas las parejas que tienen problemas de fertilidad, siendo causas importantes, la astenozoospermia y la oligozoospermia. Resultados obtenidos por nuestro grupo, bloqueando la cadena respiratoria mitocondrial, demostraron que la motilidad espermática es dependiente del ATP mitocondrial. Diversos autores han encontrado que pacientes con diversas alteraciones mitocondriales muestran un mal funcionamiento de los órganos con gran demanda energética. Por otro lado, se ha establecido que los haplogrupos mitocondriales parecen predisponer a una mayor resistencia o susceptibilidad, según los casos, a determinadas enfermedades. Este trabajo, realizado con una población de 562 individuos procedentes de clínicas de reproducción asistida, muestra que el clado mitocondrial HV aporta un fondo genético resistente a la astenozoospermia. Además, ha podido observarse una disminución de la cantidad relativa de mtDNA conforme aumenta el porcentaje de espermatozoides progresivos y la concentración espermática. Todo ello permite afirmar que el genoma mitocondrial influye en la calidad seminal (AU)

Human mtDNA haplogroups associated with high or reduced spermatozoa motility.

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.