m.4216 T > C polymorphism in JT cluster determines a lower pregnancy rate in response to controlled ovarian stimulation treatment.

PURPOSE: To analyze the influence of Caucasian mitochondrial haplogroups on controlled ovarian stimulation outcome (COS), embryo (E), and pregnancy success. METHODS: In a Caucasian population (n = 517) undergoing COS, mitochondrial haplogroups and physiological parameters were determined. Patients were classified, according to Bologna criteria, as good (>3)/poor ≤3) responder, on dependence of recruited oocytes (RO), and in pregnancy/non-pregnancy groups. Haplogroups were determined by sequencing mitochondrial hypervariable sequence I and confirmed by polymerase chain reaction (PCR), followed by restriction fragment length polymorphisms (RFLP). RESULTS: The rank of total dose of FSH (TD FSH) was similar in all clusters/haplogroups, except in JT, which is narrower (950-3,650 IU), particularly in T (1,350-3,650 IU). The statistical analysis showed higher RO and E in JT when compared to U, although it was only Uk which accumulated significantly in pregnancy respect to JT. Pearson's correlations between TD FSH and RO showed negative statistical significance in all population (P = 0.001), H (P = 0.03), JT (P = 0.01), and T (P = 0.03). The percentage of contribution of TD FSH on RO was almost nine times in the JT cluster as compared to all population one. CONCLUSIONS: JT cluster shows a different influence of TD FSH on RO. JT cluster shows higher RO and E than U, but it is Uk which exhibits a significant higher pregnancy rate than JT. The negative influence of the JT cluster on pregnancy success strongly suggests that the m.4216 T > C polymorphism could be responsible.

Variants Ala307Ala and Ser680Ser of 307 and 680 FSHr polymorphisms negatively influence on assisted reproductive techniques outcome and determine high probability of non-pregnancy in Caucasian patients.

PURPOSE: To determine the influence of different genotypes of Ala307Thr and Asn680Ser FSHr polymorphisms on controlled ovarian stimulation (COS) outcome and pregnancy. METHODS: This study collected blood and physiological and clinical parameters of 517 Caucasian patients (Statistical power ≥ 80%) that underwent COS treatment. Genotypes of Ala307Thr and Asn680Ser polymorphisms were determined using PCR amplification followed by Bsu36I and BsrI digestion, respectively. RESULTS: Ala307Ala and Ser680Ser genotypes associated to worse parameters of COS outcome (preovulatory follicles P = 0.05, in both), justifying their lower pregnancy rate than Non-Ala307Ala, P = 0.01 and Non-Ser680Ser, P = 0.004, respectively or together, (P = 0.003). Within the Non-Ala307Ala group, Thr307Thr genotype showed higher number of fertilized oocytes (P = 0.04) and embryos (P = 0.01) than Non-Thr307Thr, but no influence on pregnancy rate. Ala307Ala and Ser680Ser patients doubled probability of non-pregnancy than Non-Ala307Ala (odds ratio = 2.0) and Non-Ser680Ser (odds ratio = 2.11), respectively. Ala307Ala and Ser680Ser genotypes tend to appear together (P < 0.0001), which increases the probability of non-pregnancy. CONCLUSIONS: Ala307Ala and Ser680Ser genotypes of 307 and 680 FSHr polymorphisms associate to worse COS outcome than its respective Non-Ala307Ala and Non-Ser680Ser. Within the Non-Ala307Ala genotypes, Thr307Thr, although shows higher Fertilized Oocytes and Embryos, do not influence on pregnancy rate. Ala307Ala and Ser680Ser genotypes double the probability of Non-Pregnancy than their respective Non-Ala307Ala and Non-Ser680Ser genotypes. Furthermore, the strong tendency of these genotypes to appear together worsens the probability of pregnancy in these patients.

Influences of physical fitness on bone mass in women with fibromyalgia.

The aim of this study was to provide information about the relationship of bone mineral content (BMC) and density (BMD) with some physical-fitness-related variables in a sample of women with fibromyalgia (FM) and age-matched women without FM. Twenty-eight women clinically diagnosed with FM (age 51.1 ± 8.4 yr, M ± SD) and 22 age-matched controls participated in the study. Whole-body BMC and BMD, lean mass, handgrip strength, quadriceps strength, and cardiovascular fitness were measured in all participants. The association between physical-fitness variables and bone-related variables was tested by linear regression controlling for body weight as a possible confounder. There were no differences in BMC or BMD between groups. Women with FM had lower values of handgrip strength, quadriceps strength, and VO2peak than the control group. Handgrip strength and aerobic capacity were associated with BMC and BMD and quadriceps strength was associated with BMD in women with FM; however, only VO2peak was associated with BMC in the group of women without FM. Bone mass of women with FM may be more susceptible to changes in physical fitness than that of the women without fibromyalgia.

Increased intrinsic mitochondrial function in humans with mitochondrial haplogroup H.

It has been suggested that human mitochondrial variants influence maximal oxygen uptake (VO2max). Whether mitochondrial respiratory capacity per mitochondrion (intrinsic activity) in human skeletal muscle is affected by differences in mitochondrial variants is not known. We recruited 54 males and determined their mitochondrial haplogroup, mitochondrial oxidative phosphorylation capacity (OXPHOS), mitochondrial content (citrate synthase (CS)) and VO2max. Intrinsic mitochondrial function is calculated as mitochondrial OXPHOS capacity divided by mitochondrial content (CS). Haplogroup H showed a 30% higher intrinsic mitochondrial function compared with the other haplo group U. There was no relationship between haplogroups and VO2max. In skeletal muscle from men with mitochondrial haplogroup H, an increased intrinsic mitochondrial function is present.

Influencia de las variantes genéticas y genómicas mitocondriales en la práctica deportiva / Influence of genomic and genetic mitochondrial variants on sport practice

La mitocondria. Es un orgánulo celular que aporta la mayor parte de la energía celular. Presenta genoma propio, pequeño, con alta tasa de mutación y heredado por línea materna, del que se conocen variantes geográficas no patológicas, los haplogrupos mitocondriales. Efecto de las variantes genéticas. Al menos en haplogrupos caucásicos, el fondo genético mitocondrial influye en el VO2max, aunque el entrenamiento parece enmascarar este efecto. Los haplogrupos H (más eficiente energéticamente) y J(menos eficiente) son los que presentan los valores máximo y mínimo de consumo de oxígeno, respectivamente, lo quepodría resultar paradójico si se olvida que el oxígeno total incluye el consumido en la cadena respiratoria y el utilizado en la producción de radicales libres. Esta elevada producción en H justificaría el mayor daño oxidativo muscular encontrado respecto a J. En su conjunto, las características bioquímicas de los haplogrupos sugieren que, en pruebas cortas e intensas, el haplogrupo H podría resultar ventajoso al aportar más ATP, aunque a causa del mayor daño oxidativo inducido, el proceso de recuperación fuese más largo. Efecto de la dosis genómica mitocondrial (copias del genoma mitocondrial/célula). Se sabe que la dosis genómica mitocondrial varía según las necesidades energéticas de las células, siendo las fibras musculares, hepatocitos y neuronas lasque presentan valores más altos. Estudiado el efecto del entrenamiento regular, sobre todo aeróbico, se ha observado un aumento en la dosis genómica mitocondrial como adaptación a una elevada y continuada demanda de ATP. Sin embargo, las pruebas físicas de intensidad media-alta, en condiciones de deshidratación e hipertermia, inducen una caída significativa de la dosis genómica mitocondrial, debido al intenso daño oxidativo generado, lo que a su vez desencadenaría la intensa fatiga del deportista. Los trabajos sobre el tiempo necesario para recuperar la dosis genómica mitocondrial inicial se estiman entre las 48-72 horas (AU)

Mitochondrion. It is a cellular organelle that provides the most part of cellular energy. This organelle presents a small genome, with high rate of mutation, inherited by maternal line and which shows geographical non-pathological variants, the mitochondrial haplogroups. Effect of genetic variants. At least in Caucasians haplogroups, mitochondrial genetic background influences on VO2max, although the training seems to mask this effect. Haplogroups H (more energy efficient) and J (less efficient) are those with the maximum and minimum values of oxygen consumption, respectively, which may seem paradoxical if it is forgotten that total oxygen includes those consumed in the respiratory chain, besides those used in the free radicals production. This high production in H would justify greater muscle oxidative damage found in respect to J. Taken together, the biochemical characteristics of the haplogroups suggest that in short-intense physical exercise, haplogroup H may be advantageous to provide more ATP, but, because of higher induced oxidative damage, the recovery process would be longer.Eff ect of mitochondrial genomics dose (mitochondrial genome copies/cell). It is known that mitochondrial genomics dose varies on dependence of the energy needs of the cells, being muscle fibers, hepatocytes and neurons those that show higher values. Studied the effect of regular training, particularly aerobic, there has been observed an increase in mitochondrial genomic dose as adaptation to continued high ATP demand. However, a bout of medium-high intensity physical exercise, under conditions of dehydration and hyperthermia, induced a significant drop in mitochondrial genomic dose, probably due to intense oxidative damage, which in turn triggers the intense fatigue of the athlete. Works on the recovery time of the initial mitochondrial genomics dose were estimated between 48-72 hours (AU)

Effect of endurance and resistance training on regional fat mass and lipid profile.

The purpose of this study was to investigate the effect of 10-week of endurance training or resistance training on regional and abdominal fat, and in the lipid profile, examining the associations among the changes in body composition, weight, waist circumference and lipid profile. Body composition, waist circumference and lipid profile were analyzed in 26 volunteers healthy young men (age 22.5 ± 1.9 yr), randomly assigned to: endurance group (EG), resistance group (RG) or control group (CG). The EG significantly decreased after training the body weight, body mass index, total body fat and percentage of fat, fat and percentage of fat at the trunk and at the abdominal region and High-Density Lipoprotein. The RG significantly increased total lean mass and decreased total cholesterol, High-Density and Low- Density Lipoprotein. Close relationship were found among changes in weight, total lean mass, regional fat mass, waist circumference and changes in lipid profile (all p < 0.05). We concluded that 10-week of endurance training decreased abdominal and body fat in young men, while 10-week of resistance training increased total lean mass. These types of training had also effects on lipid profile that seem to be to some extent associated to changes in body composition; however it requires additional investigation.

El objetivo de este estudio fue investigar el efecto de 10 semanas de entrenamiento de resistencia ó fuerza sobre la cantidad de grasa en la región abdominal y sobre el perfil lipídico, analizando las asociaciones entre los cambios en composición corporal, peso, circunferencia de la cintura y perfil lipídico. La composición corporal, la circunferencia de la cintura y el perfil lipídico fueron analizados en 26 jóvenes (edad 22.5 ± 1,9 AÑOs), que se asignaron aleatoriamente a un grupo de resistencia (EG), un grupo de fuerza (RG) o al grupo control (CG). El EG disminuye significativamente, después del entrenamiento, el peso corporal, el índice de masa corporal, la cantidad total de grasa y el porcentaje de grasa, la grasa y porcentaje de grasa en el tronco y en la región abdominal y la lipoproteina de alta densidad. El RG mejoró significativamente la masa muscular total y disminuyeron el colesterol total, HDL y LDL. Se observó una relación estrecha entre los cambios en el peso, la masa magra total, la masa grasa regional, la cintura de la cadera y los cambio lipídicos (p < 0,05). Concluimos que 10 semanas de entrenamiento de resistencia disminuyen la grasa abdominal y corporal en sujetos jóvenes, mientras que 10 semanas de entrenamiento de fuerza aumentan la masa muscular total. Estos entrenamientos tienen un efecto sobre el perfil lipídico que parecen estar asociado a cambios en la composición corporal, no obstante, son necesarios más estudios.

Effect of endurance and resistance training on regional fat mass and lipid profile / Efecto del entrenamiento de resistencia y fuerza sobre la masa grasa regional y el perfil lípido

The purpose of this study was to investigate the effect of 10-week of endurance training or resistance training on regional and abdominal fat, and in the lipid profile, examining the associations among the changes in body composition, weight, waist circumference and lipid profile. Body composition, waist circumference and lipid profile were analyzed in 26 volunteers healthy young men (age 22.5 ± 1.9 yr), randomly assigned to: endurance group (EG), resistance group (RG) or control group (CG). The EG significantly decreased after training the body weight, body mass index, total body fat and percentage of fat, fat and percentage of fat at the trunk and at the abdominal region and High-Density Lipoprotein. The RG significantly increased total lean mass and decreased total cholesterol, High-Density and Low-Density Lipoprotein. Close relationship were found among changes in weight, total lean mass, regional fat mass, waist circumference and changes in lipid profile (all p < 0.05). We concluded that 10-week of endurance training decreased abdominal and body fat in young men, while 10-week of resistance training increased total lean mass. These types of training had also effects on lipid profile that seem to be to some extent associated to changes in body composition; however it requires additional investigation (AU)

El objetivo de este estudio fue investigar el efecto de 10 semanas de entrenamiento de resistencia ó fuerza sobre la cantidad de grasa en la región abdominal y sobre el perfil lipídico, analizando las asociaciones entre los cambios en composición corporal, peso, circunferencia de la cintura y perfil lipídico. La composición corporal, la circunferencia de la cintura y el perfil lipídico fueron analizados en 26 jóvenes (edad 22.5 ± 1,9 años), que se asignaron aleatoriamente a un grupo de resistencia (EG), un grupo de fuerza (RG) o al grupo control (CG). El EG disminuye significativamente, después del entrenamiento, el peso corporal, el índice de masa corporal, la cantidad total de grasa y el porcentaje de grasa, la grasa y porcentaje de grasa en el tronco y en la región abdominal y la lipoproteina de alta densidad. El RG mejoró significativamente la masa muscular total y disminuyeron el colesterol total, HDL y LDL. Se observó una relación estrecha entre los cambios en el peso, la masa magra total, la masa grasa regional, la cintura de la cadera y los cambio lipídicos (p < 0,05). Concluimos que 10 semanas de entrenamiento de resistencia disminuyen la grasa abdominal y corporal en sujetos jóvenes, mientras que 10 semanas de entrenamiento de fuerza aumentan la masa muscular total. Estos entrenamientos tienen un efecto sobre el perfil lipídico que parecen estar asociado a cambios en la composición corporal, no obstante, son necesarios más estudios (AU)

Unmasking the causes of multifactorial disorders: OXPHOS differences between mitochondrial haplogroups.

Many epidemiologic studies have associated human mitochondrial haplogroups to rare mitochondrial diseases like Leber's hereditary optic neuropathy or to more common age-linked disorders such as Parkinson's disease. However, cellular, biochemical and molecular-genetic evidence that is able to explain these associations is very scarce. The etiology of multifactorial diseases is very difficult to sort out because such diseases are due to a combination of genetic and environmental factors that individually only contribute in small part to the development of the illness. Thus, the haplogroup-defining mutations might behave as susceptibility factors, but they could have only a small effect on oxidative phosphorylation (OXPHOS) function. Moreover, these effects would be highly dependent on the 'context' in which the genetic variant is acting. To homogenize this 'context' for mitochondrial DNA (mtDNA) mutations, a cellular approach is available that involves the use of what is known as 'cybrids'. By using this model, we demonstrate that mtDNA and mtRNA levels, mitochondrial protein synthesis, cytochrome oxidase activity and amount, normalized oxygen consumption, mitochondrial inner membrane potential and growth capacity are different in cybrids from the haplogroup H when compared with those of the haplogroup Uk. Thus, these inherited basal differences in OXPHOS capacity can help to explain why some individuals more quickly reach the bioenergetic threshold below which tissue symptoms appear and progress toward multifactorial disorders. Hence, some population genetic variants in mtDNA contribute to the genetic component of complex disorders. The existence of mtDNA-based OXPHOS differences opens possibilities for the existence of a new field, mitochondrial pharmacogenomics. New sequence accession nos: HM103354-HM103363.

Human mitochondrial haplogroup H: the highest VO2max consumer--is it a paradox?

Mitochondrial background has been demonstrated to influence maximal oxygen uptake (VO(2max), in mLkg(-1)min(-1)), but this genetic influence can be compensated for by regular exercise. A positive correlation among electron transport chain (ETC) coupling, ATP and reactive oxygen species (ROS) production has been established, and mitochondrial variants have been reported to show differences in their ETC performance. In this study, we examined in detail the VO(2max) differences found among mitochondrial haplogroups. We recruited 81 healthy male Spanish Caucasian individuals and determined their mitochondrial haplogroup. Their VO(2max) was determined using incremental cycling exercise (ICE). VO(2max) was lower in J than in non-J haplogroup individuals (P=0.04). The H haplogroup was responsible for this difference (VO(2max); J vs. H; P=0.008) and this group also had significantly higher mitochondrial oxidative damage (mtOD) than the J haplogroup (P=0.04). In agreement with these results, VO(2max) and mtOD were positively correlated (P=0.01). Given that ROS production is the major contributor to mtOD and consumes four times more oxygen per electron than the ETC, our results strongly suggest that ROS production is responsible for the higher VO(2max) found in the H variant. These findings not only contribute to a better understanding of the mechanisms underneath VO(2max), but also help to explain some reported associations between mitochondrial haplogroups and mtOD with longevity, sperm motility, premature aging and susceptibility to different pathologies.

Moroccan mitochondrial genetic background suggests prehistoric human migrations across the Gibraltar Strait.

Migrations into Africa from the Levant have greatly determined the mitochondrial genetic landscape of North Africa. After analyzing samples from North Morocco to Spain, we show that three fourths of the Moroccan individuals belong to Western Eurasian haplogroups and the frequencies of these are much more similar to those of the Iberian Peninsula than to those of the Middle East. This is particularly true for the mitochondrial haplogroups H1, H3 and V, which experienced a late-glacial expansion from this region, that repopulated much of Central and Northern Europe. Iberian Peninsula was also a source for prehistoric migrations to North Africa.

Steady exercise removes VO(2max) difference between mitochondrial genomic variants.

It has been clearly established that mitochondrial variants, among other potential factors, influence on VO(2max). With this study we sought to determine whether this genetic predisposition could be modified by steady exercise. Mitochondrial genetic variants were determined in 70 healthy controls (CON) and in 77 athletes who trained regularly (50 cyclists, aerobic training (AER), and 27 runners of 400m, anaerobic training (NoAER)). All of them were male Spanish Caucasian individuals. A maximum graded exercise test (GXT) in cycle-ergometer was performed to determine VO(2max) (mL kg(-1)min(-1)). Our results confirmed that, in CON, VO(2max) (P=0.007) was higher in Non-J than J individuals. Furthermore, we found that AER and NoAER showed, as it could be expected, higher VO(2max) than CON, but not differences between mitochondrial variants have been found. According with these findings, the influence of mitochondrial DNA (mtDNA) variants on VO(2max) has been confirmed, and a new conclusion has arisen: the steady exercise is able to remove this influence. The interest of these promising findings in muscular performance should be further explored, in particular, the understanding of potential applications in sport training and in muscle pathological syndromes.

Human mitochondrial variants influence on oxygen consumption.

This work investigates if human mitochondrial variants influence on maximal oxygen consumption (VO(2max)). With this purpose we recruited, as a uniform population in term of nutritional habits and life style, 114 healthy male Spanish subjects that practiced fitness exercises 3-4 times a week. Once mtDNA haplogroups were determined, we found that J presents with lower VO(2max) (P=0.02) than nonJ variants. J has been related with a lower efficiency of electron transport chain (ETC), diminished ATP and ROS production. Thus, the difficult to compensate the mitochondrial energetic deficiency could explain the accumulation of J haplogroup in LHON and multiple sclerosis. Furthermore, the lower ROS production associated to J could also account for the accrual of this variant in elderly people consequent to a decreased oxidative damage.

20 years of human mtDNA pathologic point mutations: carefully reading the pathogenicity criteria.

Despite the strong purifying selection that occurs during embryonic development, the particular location and features of mitochondrial DNA make it especially susceptible to accumulating point mutations, giving rise to a large number of mitochondrial DNA variants. Many of these will have moderate or no phenotypic effects but others will be the cause of very dramatic diseases, usually known as mitochondriopathies. Because of the abundance of different mitochondrial DNA variants, it is not easy to determine whether a new mutation is pathogenic. To facilitate this task, different criteria have been proposed, but they are often either too severely or too loosely applied. Citing examples from the literature, in this paper we discuss some critical aspects of these criteria.

Association of mitochondrial haplogroup J and mtDNA oxidative damage in two different North Spain elderly populations.

This work investigates the association between longevity, mitochondrial DNA (mtDNA) variants and oxidative DNA damage in an older than 85 years population. The participants, similar in genetic and cultural background as well as gender distribution, come from villages near to the Pyrenees Mountains (900-1,400 m altitude) (n = 69) and the Ebro's Valley (200-300 m altitude) (n = 69) in Spain. Our results show an accumulation of the haplogroup J in elderly individuals with an over-representation of J2 in Pyrenees group but not in the Ebro's Valley, the former associating with a diminished DNA damage. In conclusion, our results suggest that J mitochondrial variant, that induce lower mtDNA damage, could present a phenotypic survival advantage to environmental conditions and, thus, accumulate in elderly population.

Diseases of the human mitochondrial oxidative phosphorylation system.

Mitochondrial diseases, or diseases of the oxidative phosphorylation system, consist of a group of disorders originated by a deficient synthesis of ATP. This system is composed of proteins codified in the two genetic systems of the cell, the nuclear and the mitochondrial genomes, and, therefore, the mode of inheritance could be either mendelian or maternal. The diseases can also appear sporadically. Due to the central role that mitochondria play in cellular physiology, these diseases are a social and health problem of great importance. They are considered rare diseases; however, together they constitute a large variety of genetic disorders. It is also believed that mitochondria are involved, directly or indirectly, in many other human diseases, mainly in age-related diseases. This review will focus mainly on describing the special characteristics of the mitochondrial genetic system and the diseases caused by mitochondrial DNA mutations. We will also note the difficulties in studying these pathologies, and the possible involvement of the genetic variability of the mitochondrial genome in the development of these diseases.

Association of human mitochondrial DNA variants with plasma LDL levels.

Increasing evidence supports the relationship between mitochondrial DNA variability and differences in energy metabolism, which may have pathophenotypic consequences. MtDNA pathological mutation has been also described to be associated with hypercholesterolemia. The target of this work consisted in studying the possible existence of an association between the mitochondrial DNA variability and plasma cholesterol levels. For this, two populations of 61 sedentary and 83 sportsmen were used to estimate the association of the lipidemic levels with the mitochondrial DNA variant harboured by them. Triglycerides, HDL-c, LDL-c and cholesterol/HDL-c were essayed, and mitochondrial DNA polymorphisms were assessed by HVR I sequencing and PCR/RFLP analysis. Major Caucasian mtDNA clades (HV, JT, U and IWX) did not associate with lipidemic levels in the sedentary population. However, in the case of a more disciplined population in term of nutritional habits and life style as sportsmen are, a significantly higher and lower level of LDL-c was associated with HV and JT clade, respectively. This observation could have relevant significance for metabolic distress diseases affecting plasma cholesterol levels.

The role of the mitochondrion in sperm function: is there a place for oxidative phosphorylation or is this a purely glycolytic process?

We review here the current knowledge related to the metabolic pathways used by spermatozoa to meet their high demands for ATP. This is discussed with special emphasis on one of their key roles, motility. We believe that the controversy among glycolytic and oxidative phosphorylation supporters is artificial and, as it happens in many other cell types, the source of ATP is multiple and depends on external inputs.

Mitochondrial lineages distribution in the Spanish population: anticipating association studies

La variación genética en el mtDNA ha sido ampliamente utilizada para dar una perspectiva de la historia demográfica humana. En este estudio, nosotros hemos analizado esta variabilidad en 686 muestras del Centro y Norte de España. La frecuencia de los haplogrupos en la población española es muy similar a la observada en otros estudios sobre esta población y a las frecuencias en las poblaciones europeas. Un análisis más profundo del haplogrupo mitocondrial U mostró diferencias con las poblaciones del norte de Europa. El conocimiento de la distribución de frecuencias de los haplogrupos en nuestra población supone un resultado importante para el diseño de estudios sobre enfemedades mitocondriales. Además, nuestros resultados son también importantes en los estudios forenses

The genetic variation in mtDNA has been widely used to give a maternal genetic perspective of the human demographic history. Here, we have studied this variability in 686 samples coming from the Centre and North of Spain. These results showed that haplogroup frequencies were similar to other Spanish studies and European populations. Haplogroups from the HV lineage were over-represented in the Spanish population. A deeper analysis of the mitochondrial haplogroup U showed differences with Northern Europe populations. The frequencies of haplogroups found give them high valour when experimental design for mitochondrial disorder studies in population is planted. In addition, the use of these data is also important for forensic studies

Differences of sperm motility in mitochondrial DNA haplogroup U sublineages.

We had previously shown that sperm from men harbouring haplogroup T mtDNAs swim less vigorously than those from haplogroup H. However, the biochemical basis of this motility was difficult to investigate because of the multiple mutations, the most important of which affected respiratory complex I for which there is no crystal structure. To more thoroughly study the relationship between mtDNA variation and differences in mitochondrial energy metabolism, we turned to the analysis of sperm baring haplogroup U mtDNAs. Haplogroup U is a monophyletic ancient and thus heterogeneous maternal lineage that is broadly distributed among European individuals. Several sublineages of haplogroup U were found to be associated with differences in sperm motility and vitality. These differences could be related to a highly conserved missense mutation in the mtDNA COIII gene (V91) and several equally conserved mutations in the cytochrome b (cytb) gene. Moreover, the lineages with the cytb mutations were substantially enriched in northern Europe, while those lacking these mutations were more prevalent in southern Europe. We suggest that some of these ancient conserved cytb missense mutations permitted our ancestors to adapt to cold by partially uncoupling mitochondrial oxidative phosphorylation (OXPHOS).

Mitochondria from ejaculated human spermatozoa do not synthesize proteins.

Sperm motility is dependent on mitochondrial ATP production that relies on the coordinated expression of the mitochondrial and nuclear genomes. It is generally accepted that mammalian ejaculated spermatozoa retain the ability to synthesize mtDNA-encoded proteins but not most of the nuclear ones. This implies an asynchronous regulation of the oxidative phosphorylation-related genes encoded by each genome. Trying to investigate this issue, we unexpectedly found that ejaculated human spermatozoa do not synthesize mtDNA-encoded proteins. Moreover, we estimated that the discrepancy between our observations and those published elsewhere was due to a chloramphenicol-sensitive protein synthesis attributed to mitochondria that instead corresponds to contaminating bacteria.