Reply to : Proofreading deficiency in mitochondrial DNA polymerase does not affect total dNTP pools in mouse embryos

Non peer reviewe

mtDNA Mutagenesis Disrupts Pluripotent Stem Cell Function by Altering Redox Signaling

mtDNA mutagenesis in somatic stem cells leads to their dysfunction and to progeria in mouse. The mechanism was proposed to involve modification of reactive oxygen species (ROS)/redox signaling. We studied the effect of mtDNA mutagenesis on reprogramming and stemness of pluripotent stem cells (PSCs) and show that PSCs select against specific mtDNA mutations, mimicking germline and promoting mtDNA integrity despite their glycolytic metabolism. Furthermore, mtDNA mutagenesis is associated with an increase in mitochondrial H2O2, reduced PSC reprogramming efficiency, and self-renewal. Mitochondria-targeted ubiquinone, MitoQ, and N-acetyl-L-cysteine efficiently rescued these defects, indicating that both reprogramming efficiency and stemness are modified by mitochondrial ROS. The redox sensitivity, however, rendered PSCs and especially neural stem cells sensitive to MitoQ toxicity. Our results imply that stem cell compartment warrants special attention when the safety of new antioxidants is assessed and point to an essential role for mitochondrial redox signaling in maintaining normal stem cell function.Peer reviewe

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

Substitute or addition to hypermobile lifestyles? Second home mobility and Finnish CO 2

Tourism produces an increasing share in global greenhouse gas (GHG) emissions. These are mostly derived from transport emissions, and long-haul air travel in particular. Short-haul domestic tourism is believed by some to be a potential substitute for long-haul tourism. Using the example of Finland this paper examines the extent to which domestic second home tourism can substitute for other leisure trips and therefore contribute to reductions of travel-generated GHG emissions. Survey data are used to evaluate the CO2 emissions caused by travel to domestic second homes, and to create statistical models that verify if the owners of domestic second homes travel to other leisure destinations less frequently than others, and if they cause less emissions by their leisure mobility than others with comparable economic and demographic background. We find that although the owners and users of domestic second homes travel for other leisure purposes less frequently than others, this does not mean their leisure mobility generates less emissions. Overall, owners of second homes produce significantly more CO2 by their leisure mobility than non-owners. The use of second homes does not seem to be a substitute for high emission long-haul travels, but rather a part of an overall highly mobile leisure lifestyle. It is therefore necessary to better understand and influence the entire range of individual mobility behaviours in order to reduce travel-related GHG emissions

Genetic studies of body mass index yield new insights for obesity biology

Note: A full list of authors and affiliations appears at the end of the article. Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P 20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.</p