MidA is a putative methyltransferase that is required for mitochondrial complex I function

10 páginas, 6 figuras.-- et al.Dictyostelium and human MidA are homologous proteins that belong to a family of proteins of unknown function called DUF185. Using yeast two-hybrid screening and pull-down experiments, we showed that both proteins interact with the mitochondrial complex I subunit NDUFS2. Consistent with this, Dictyostelium cells lacking MidA showed a specific defect in complex I activity, and knockdown of human MidA in HEK293T cells resulted in reduced levels of assembled complex I. These results indicate a role for MidA in complex I assembly or stability. A structural bioinformatics analysis suggested the presence of a methyltransferase domain; this was further supported by site-directed mutagenesis of specific residues from the putative catalytic site. Interestingly, this complex I deficiency in a Dictyostelium midA- mutant causes a complex phenotypic outcome, which includes phototaxis and thermotaxis defects. We found that these aspects of the phenotype are mediated by a chronic activation of AMPK, revealing a possible role of AMPK signaling in complex I cytopathology.This work was supported by grants BMC2006-00394 and BMC2009-09050 to R.E. from the Spanish Ministerio de Ciencia e Innovación; to P.R.F. from the Thyne Reid Memorial Trusts and the Australian Research Council; to A.V. and O.G. from the Spanish National Bioinformatics Institute (www.inab.org), a platform of Genome Spain; to R.G. from the Fondo de Investigaciones Sanitarias, Instituto de Salud Carlos III, Spain (PI070167) and from the Comunidad de Madrid (GEN-0269/2006). S.C. is supported by a research contract from Consejería de Educación de la Comunidad de Madrid y del Fondo Social Europeo (FSE).Peer Reviewe

Riblets Induced Drag Reduction on a Spatially Developing Turbulent Boundary Layer

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A warm and humid paleoecological context for the Neanderthal mountain settlement at the Navalmaíllo rockshelter (Iberian Central System, Madrid)

Neanderthals have been claimed to have had a selective adaptation to rugged, wooded landscapes that would have partially compensate their high basal metabolic rate and locomotor energetic costs through reducing search time and increasing diet breadth. The archaeological site of the Navalmaíllo rockshelter (Pinilla del Valle, Madrid), located in a mountain environment in central Iberian Peninsula, has been interpreted as a repeated short-term occupation hunting camp by Neanderthal groups, mainly focused on primary access to large bovids and cervids. Navalmaíllo rockshelter has also furnished fish, toads, frogs, tortoises, lizards and snakes remains. This association of amphibians and reptiles suggests a much warmer climate (+2.8 °C) for layer F than at present, with similar temperatures during the summer but higher temperatures throughout the remaining months. Rainfall was slightly more abundant (+180.6 mm) than today, with a more contrasted regime during the year, with rainier winters and drier summers. A two-month period of aridity is observed during summer, representing a similar duration to present-day climatic conditions. Reconstructed landscapes are mainly constituted by open areas with dry grassland and rocky or stony areas, evolving laterally to humid meadows, probably close to the aquatic and peri-aquatic areas, such as rivers or ponds with riverside vegetation. Woodland environments are also well represented around the site, with medium scrublands to forest formations. Fish complete this reconstruction by documenting the presence of a pre-mountain well-developed river system characterized by relatively cold, permanent, oxygen-rich, and running waters. Such reconstruction is in disagreement with previous pollen interpretation for Layer F that suggested a very open and cold environment. Our new interpretation suggests that the Neanderthal occupation of the Navalmaíllo rockshelter occurred during a somewhat temperate and humid period, probably within the later part of the Marine Isotope Stage 5, effectively favouring the presence of a high biodiversity around the site