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Eukaryotic cells typically contain numerous mitochondria, each with multiple copies of their own genome, the mtDNA. Uniparental transmission of mitochondria, usually via the mother, prevents the mixing of mtDNA from different individuals. While on the one hand, this should resolve the potential for selection for fast-replicating mtDNA variants that reduce organismal fitness, maternal inheritance will, in theory, come with another set of problems that are specifically relevant to males. Maternal inheritance implies that the mitochondrial genome is never transmitted through males, and thus selection can target only the mtDNA sequence when carried by females. A consequence is that mtDNA mutations that confer male-biased phenotypic expression will be prone to evade selection, and accumulate. Here, we review the evidence from the ecological, evolutionary and medical literature for male specificity of mtDNA mutations affecting fertility, health and ageing. While such effects have been discovered experimentally in the laboratory, their relevance to natural populations—including the human population—remains unclear. We suggest that the existence of male expression-biased mtDNA mutations is likely to be a broad phenomenon, but that these mutations remain cryptic owing to the presence of counter-adapted nuclear compensatory modifier mutations, which offset their deleterious effects.

Ignacio Ballester Pardo conversa con la escritora venezolana María Auxiliadora Álvarez al hilo de algunos temas planteados en este dossier de Mitologías hoy.

El principal propósito de esta investigación fue la detección y el análisis del grado de presencia de falsas creencias relacionadas con la actividad física y el deporte en una muestra estudiantes en formación de esta materia. Dicha muestra estuvo compuesta por un total de 105 estudiantes pertenecientes a las titulaciones de Técnico de Conducción de Actividades Físicas en el Medio Natural y Técnico Superior de Enseñanza y Animación Sociodeportiva. La recogida de datos se llevó a cabo mediante la administración telemática del cuestionario validado de Hábitos Deportivos y Alimenticios. Los resultados arrojaron un alto grado de prevalencia de falsas creencias. Destacan, como errores más extendidos, las creencias de que “la natación estilos es eficiente en la rehabilitación de problemas de espalda”, “al trabajar los abdominales podemos diferenciar entre ejercicios para abdominales superiores e inferiores”, “el consumo de té verde y/o la L-Carnitina favorece la pérdida de peso (oxidación de las grasas)” y “al realizar un ejercicio de mayor intensidad, la quema de grasas aumenta”. Además, podemos afirmar, que una gran mayoría de los errores, se dan dentro de las preguntas con relación al entrenamiento de fuerza. Con respecto al nivel formativo, se ha observado una disminución del grado de prevalencia de estas falsas creencias a lo largo del proceso formativo. No se apreciaron diferencias significativas en cuanto a las respuestas dada en función del sexo. Como conclusión, se ha encontrado un alto grado de desconocimiento en muchos de estos mitos , encontrándose cerca del 50% de las falsas concepciones ampliamente arraigadas entre la muestra. Palabras clave: falsas creencias, salud , ejercicio físico,  formación Abstract. The main purpose of this research was to detect and analyze the degree of presence of misconceptions and false beliefs related to physical activity and sport in a sample of students in this area of studies. The sample was made up of a total of 105 students in non-university higher education. Data collection was carried out through the telematic administration of the validated questionnaire “Sport and Food Habits”. Results showed a high degree of prevalence of misconceptions raised in the questionnaire, since almost 50% of false conceptions are widely rooted among the sample. It should be noted that amongst the most widespread misconceptions we find the following: “swimming is efficient in the rehabilitation of back problems”, “when we train abdominal area, we can differentiate between exercises for upper and lower abdominals”, “the consumption of Green tea and/or L-Carnitine favors weight loss (fat oxidation)” and “when we train more intensely, fat burning increases”. Furthermore, we noticed that most misconceptions are found in strength training questions. A decrease in the degree of prevalence of these false beliefs has been observed in relation to higher education levels. There were no significant differences in terms of the answers given according to the participant´s sex. In conclusion, a high degree of misinformation (nearly 50%) was found amongst the students. Keywords: misconception, health, false belief, physical activity, training.

The mechanisms involved in the production of red carotenoid-based ornaments of vertebrates are still poorly understood. These colorations often depend on enzymatic transformations (ketolation) of dietary yellow carotenoids, which could occur in the inner mitochondrial membrane (IMM). Thus, carotenoid ketolation and cell respiration could share biochemical pathways, favoring the evolution of ketocarotenoid-based ornaments as reliable indices of individual quality under sexual selection. Captive male red crossbills (Loxia curvirostra Linnaeus) were exposed to redox-active compounds designed to penetrate and act in the IMM: an ubiquinone (mitoQ) or a superoxide dismutase mimetic (mitoTEMPO). MitoQ can act as an antioxidant but also distort the IMM structure, increasing mitochondrial free radical production. MitoQ decreased yellow carotenoids and tocopherol levels in blood, perhaps by being consumed as antioxidants. Contrarily, mitoTEMPO-treated birds rose circulating levels of the second most abundant ketocarotenoid in crossbills (i.e., canthaxanthin). It also increased feather total red ketocarotenoid concentration and redness, but only among those birds exhibiting a redder plumage at the start of the study, that is, supposedly high-quality individuals. The fact that mitoTEMPO effects depended on original plumage color suggests that the red-ketocarotenoid-based ornaments indicate individual quality as mitochondrial function efficiency. The findings would thus support the shared pathway hypothesis.

The best-known hallmarks of Parkinson’s disease (PD) are the motor deficits that result from the degeneration of dopaminergic neurons in the substantia nigra. Dopaminergic neurons are thought to be particularly susceptible to mitochondrial dysfunction. As such, for their survival, they rely on the elaborate quality control mechanisms that have evolved in mammalian cells to monitor mitochondrial function and eliminate dysfunctional mitochondria. Mitophagy is a specialized type of autophagy that mediates the selective removal of damaged mitochondria from cells, with the net effect of dampening the toxicity arising from these dysfunctional organelles. Despite an increasing understanding of the molecular mechanisms that regulate the removal of damaged mitochondria, the detailed molecular link to PD pathophysiology is still not entirely clear. Herein, we review the fundamental molecular pathways involved in PINK1/Parkin-mediated and receptor-mediated mitophagy, the evidence for the dysfunction of these pathways in PD, and recently-developed state-of-the art assays for measuring mitophagy in vitro and in vivo.

It has been suggested that deleterious interactions between the mitochondrial and nuclear genomes could pose a problem for mitochondrial replacement therapy (MRT). This is because the mitochondrial genome is placed in a novel nuclear environment using this technique. In contrast, it is inherited with half the mother’s genome during normal reproduction, a genome that it is relatively compatible with, since the mother is alive. Here, I review the evidence of whether mito-nuclear interactions are likely to pose a problem for MRT. The majority of the available experimental evidence, both in humans and other species, suggests that MRT is not harmful. These results are consistent with population genetic theory, which predicts that deleterious mito-nuclear interactions are unlikely to be much more prevalent in individuals born to MRT than normal reproduction, particularly in a species such as humans with low population differentiation. This is because selection is unlikely to be strong enough to establish significant linkage disequilibrium between the mitochondrial and nuclear genomes. These results are supported by a meta-analysis of 231 cases, from a variety of animals, in which the mitochondrial DNA (mtDNA) from one strain has been introgressed into the nuclear background of another strain of the same species. Overall, there is little tendency for introgression of mtDNA to be harmful.

The macrolide drug rapamycin is a benchmark anti‐ageing drug, which robustly extends lifespan of diverse organisms. For any health intervention, it is paramount to establish whether benefits are distributed equitably among individuals and populations, and ideally to match intervention to recipients' needs. However, how responses to rapamycin vary is surprisingly understudied. Here we investigate how among‐population variation in both mitochondrial and nuclear genetics shapes rapamycin's effects on lifespan. We show that epistatic “mito‐nuclear” interactions, between mitochondria and nuclei, modulate the response to rapamycin treatment. Differences manifest as differential demographic effects of rapamycin, with altered age‐specific mortality rate. However, a fitness cost of rapamycin early in life does not show a correlated response, suggesting that mito‐nuclear epistasis can decouple costs and benefits of treatment. These findings suggest that a deeper understanding of how variation in mitochondrial and nuclear genomes shapes physiology may facilitate tailoring of anti‐ageing therapy to individual need. The burden of ill health in older populations has motivated a search for anti‐ageing drugs, such as rapamycin, but are putative benefits equal among variable populations? Genes vary on DNA contained both in the nucleus and contained in mitochondria. In flies, this study demonstrates the principle that combined genetic variation in nuclei and mitochondria can interactively shape rapamycin's beneficial effects, by altering when in the lifespan the drug affects mortality.

We previously reported that delayed treatment with Mito-tempo (MT), a mitochondria-targeted superoxide dismutase mimetic, protects against the early phase of acetaminophen (APAP) hepatotoxicity by inhibiting peroxynitrite formation. However, whether this protection is sustained to the late phase of toxicity is unknown. To investigate the late protection, C57Bl/6J mice were treated with 300 mg/kg APAP followed by 20 mg/kg MT 1.5 h or 3 h later. We found that both MT treatments protected against the late phase of APAP hepatotoxicity at 12 and 24 h. Surprisingly, MT-treated mice demonstrated a significant increase in apoptotic hepatocytes, while the necrotic phenotype was observed almost exclusively in mice treated with APAP alone. In addition, there was a significant increase in caspase-3 activity and cleavage in the livers of MT-treated mice. Immunostaining for active caspase-3 revealed that the positively stained hepatocytes were exclusively in centrilobular areas. Treatment with the pan-caspase inhibitor ZVD-fmk (10 mg/kg) 2 h post-APAP neutralized this caspase activation and provided additional protection against APAP hepatotoxicity. Treatment with N-acetylcysteine, the current standard of care for APAP poisoning, protected but did not induce this apoptotic phenotype. Mechanistically, MT treatment inhibited APAP-induced RIP3 kinase expression, and RIP3-deficient mice showed caspase activation and apoptotic morphology in hepatocytes analogous to MT treatment. These data suggest that while necrosis is the primary cause of cell death after APAP hepatotoxicity, treatment with the antioxidant MT may switch the mode of cell death to secondary apoptosis in some cells. Modulation of mitochondrial oxidative stress and RIP3 kinase expression play critical roles in this switch.

Excessive mitochondrial fission following ischemia and hypoxia relies on the formation of contacts between the endoplasmic reticulum and mitochondria (ER‐Mito); however, the specific mechanisms behind this process remain unclear. Confocal microscopy and time course recording are used to investigate how ischemia and hypoxia affect the activation of dynamin‐related protein 1 (Drp1), a protein central to mitochondrial dynamics, ER‐Mito interactions, and the consequences of modifying the expression of Drp1, shroom (Shrm) 4, and inverted formin (INF) 2 on ER‐Mito contact establishment. Both Drp1 activation and ER‐Mito contact initiation cause excessive mitochondrial fission and dysfunction under ischemic‐hypoxic conditions. The activated form of Drp1 aids in ER‐Mito contact initiation by recruiting Shrm4 and promoting actin bundling between the ER and mitochondria. This process relies on the structural interplay between INF2 and scattered F‐actin on the ER. This study uncovers new roles of cytoplasmic Drp1, providing valuable insights for devising strategies to manage mitochondrial imbalances in the context of ischemic‐hypoxic injury. Activated Drp1 Initiates the formation of endoplasmic reticulum‐mitochondrial contacts via Shrm4‐Mediated Actin Bundling under ischemic‐hypoxic conditions, Drp1 activation and ER‐Mito contact initiation precede excessive mitochondrial fission and dysfunction. Activated Drp1 recruits Shrm4, promotes actin bundling between the ER and mitochondria, and relies on INF2's interaction with F‐actin on the ER. This study elucidates novel functions of cytoplasmic Drp1, offering invaluable insights for addressing the mitochondrial imbalance in ischemic‐hypoxic injury.