Caracterización de los transportadores mitocondriales de ATP-Mg/Pi y su implicación en la señalización por calcio a la mitocondria

Tesis doctoral inédita. Universidad Autónoma de Madrid, Facultad de Ciencias, Departamento de Biología Molecular. Fecha de lectura: 21-12-200

SCaMC-1 like a member of the mitochondrial carrier (MC) family preferentially expressed in testis and localized in mitochondria and chromatoid body

Mitochondrial carriers (MC) form a highly conserved family involved in solute transport across the inner mitochondrial membrane in eukaryotes. In mammals, ATP-Mg/Pi carriers, SCaMCs, form the most complex subgroup with four paralogs, SCaMC-1, -2, -3 and -3L, and several splicing variants. Here, we report the tissue distribution and subcellular localization of a mammalian-specific SCaMC paralog, 4930443G12Rik/SCaMC-1Like (SCaMC-1L), which displays unanticipated new features. SCaMC-1L proteins show higher amino acid substitution rates than its closest paralog SCaMC-1. In mouse, SCaMC-1L expression is restricted to male germ cells and regulated during spermatogenesis but unexpectedly its localization is not limited to mitochondrial structures. In mature spermatids SCaMC-1L is detected in the mitochondrial sheath but in previous differentiation stages appears associated to cytosolic granules which colocalize with specific markers of the chromatoid body (CB) in post-meiotic round spermatids and inter-mitochondrial cement (IMC) in spermatocytes. The origin of this atypical distribution was further investigated by transient expression in cell lines. Similarly to male germ cells, in addition to mitochondrial and cytosolic distribution, a fraction of SCaMC-1L-expressing COS-7 cells display cytosolic SCaMC-1L-aggregates which exhibit aggresomal-like features as the CB. Our results indicate that different regions of SCaMC-1L hinder its import into mitochondria and this apparently favours the formation of cytosolic aggregates in COS-7 cells. This mechanism could be also operational in male germ cells and explain the incorporation of SCaMC-1L into germinal granules

Aplicaciones de SIG y teledetección en ecología: Guión de prácticas de la asignatura

Este trabajo surge como resultado del Proyecto de Innovación Docente de la Universidad Autónoma de Madrid – Convocatoria 2013: Adaptación de los recursos informáticos de la asignatura “Aplicaciones de SIG y Teledetección en Ecología” del Máster Oficial en Ecología para la utilización de herramientas de software libre, y elaboración del manual de las prácticas, coordinado por Juan Traba y con la participación de Javier Seoane y Manuel B. Morales; los tres son profesores titulares del Departamento de Ecología de la Universidad Autónoma de Madrid. Ester González de Andrés ha disfrutado de una beca financiada por la la UAM durante la realización de este proyecto. Queremos agradecer expresamente la imprescindible participación de Mª Paula Delgado, Irene Guerrero y Pablo Acebes en la docencia de la asignatura, la preparación y testado de materiales y en la revisión crítica de este documento

El parásito Saprolegnia diclina (Oomycetes), otra amenaza para la conservación species Atelopus nanay

Peer Reviewe

Glucagon regulation of oxidative phosphorylation requires an increase in matrixadenine nucleotide content through Ca2+-activation of the mitochondrial ATPMg/Pi carrier SCaMC-3

13 p.-6 fig.-1 tab.It has been known for a long time that mitochondria isolated from hepatocytes treated with glucagon or Ca(2+)-mobilizing agents such as phenylephrine show an increase in their adenine nucleotide (AdN) content, respiratory activity, and calcium retention capacity (CRC). Here, we have studied the role of SCaMC-3/slc25a23, the mitochondrial ATP-Mg/Pi carrier present in adult mouse liver, in the control of mitochondrial AdN levels and respiration in response to Ca(2+) signals as a candidate target of glucagon actions. With the use of SCaMC-3 knock-out (KO) mice, we have found that the carrier is responsible for the accumulation of AdNs in liver mitochondria in a strictly Ca(2+)-dependent way with an S0.5 for Ca(2+) activation of 3.3 ± 0.9 μm. Accumulation of matrix AdNs allows a SCaMC-3-dependent increase in CRC. In addition, SCaMC-3-dependent accumulation of AdNs is required to acquire a fully active state 3 respiration in AdN-depleted liver mitochondria, although further accumulation of AdNs is not followed by increases in respiration. Moreover, glucagon addition to isolated hepatocytes increases oligomycin-sensitive oxygen consumption and maximal respiratory rates in cells derived from wild type, but not SCaMC-3-KO mice and glucagon administration in vivo results in an increase in AdN content, state 3 respiration and CRC in liver mitochondria in wild type but not in SCaMC-3-KO mice. These results show that SCaMC-3 is required for the increase in oxidative phosphorylation observed in liver mitochondria in response to glucagon and Ca(2+)-mobilizing agents, possibly by allowing a Ca(2+)-dependent accumulation of mitochondrial AdNs and matrix Ca(2+), events permissive for other glucagon actions.This work was supported in part by Ministerio de Educación y Ciencia Grants BFU2008-04084/BMC and BFU2011-30456, European Union Grant LSHMCT- 2006-518153, and CIBERER Centro de Investigaciones Biomédicas en Red de Enfermedades Raras (an initiative of the ISCIII Instituto de SaludCarlos III) (to J. S.), Comunidad de Madrid Grants S-GEN-0269-2006 and S2010/BMD-2402 MITOLAB-CM (to J. S., E. R., and A. S.), by ISCIII Grant PI080610 (to A. delA), and an institutional grant from the Fundación Ramon Areces to the Centro de Biología Molecular Severo Ochoa.Peer reviewe

Mitochondrial ATP-Mg/pi carrier SCaMC-3/Slc25a23 counteracts PARP-1-dependent fall in mitochondrial ATP caused by excitotoxic insults in neurons

Glutamate excitotoxicity is caused by sustained activation of neuronal NMDA receptors causing a large Ca2+and Na+ influx, activation of poly(ADP ribose) polymerase-1 (PARP-1), and delayed Ca2+ deregulation. Mitochondria undergo early changes in membrane potential during excitotoxicity, but their precise role in these events is still controversial. Using primary cortical neurons derived from mice, we show that NMDA exposure results in a rapid fall in mitochondrial ATP in neurons deficient in SCaMC-3/Slc25a23, a Ca2+-regulated mitochondrial ATP-Mg/Pi carrier. This fall is associated with blunted increases in respiration and a delayed decrease in cytosolic ATP levels, which are prevented by PARP-1 inhibitors or by SCaMC-3 activity promoting adenine nucleotide uptake into mitochondria. SCaMC-3 KO neurons show an earlier delayed Ca2+ deregulation, and SCaMC-3-deficient mitochondria incubated with ADP or ATP-Mg had reduced Ca2+retention capacity, suggesting a failure to maintain matrix adenine nucleotides as a cause for premature delayed Ca2+ deregulation. SCaMC-3 KO neurons have higher vulnerability to in vitro excitotoxicity, and SCaMC-3 KO mice are more susceptible to kainate-induced seizures, showing that early PARP-1-dependent fall in mitochondrial ATP levels, counteracted by SCaMC-3, is an early step in the excitotoxic cascade.This work was supported by Ministerio de Economía Grant BFU2011-30456, by Centro de Investigación Biomédica en Red de Enfermedades Raras [an initiative of the Instituto de Salud Carlos III (ISCIII)], by Comunidad de Madrid Grant S2010/BMD-2402 MITOLAB-CM (to J.S.), by ISCIII Grant PI080610 (to A.d.A.), and by an institutional grant from the Fundación Ramón Areces to the Centro de Biología Molecular Severo Ochoa. C.B.R. is the recipient of an Formacion Personal Universitario fellowship from the Ministerio de Educación y Ciencia. P.G.-S. is a recipient of a Formacion Personal Investigador-UAM fellowship from Universidad Autónoma de Madrid.Peer Reviewe

Uncovering a Novel Functional Interaction Between Adult Hepatic Progenitor Cells, Inflammation and EGFR Signaling During Bile Acids-Induced Injury

Chronic cholestatic damage is associated to both accumulation of cytotoxic levels of bile acids and expansion of adult hepatic progenitor cells (HPC) as part of the ductular reaction contributing to the regenerative response. Here, we report a bile acid-specific cytotoxic response in mouse HPC, which is partially impaired by EGF signaling. Additionally, we show that EGF synergizes with bile acids to trigger inflammatory signaling and NLRP3 inflammasome activation in HPC. Aiming at understanding the impact of this HPC specific response on the liver microenvironment we run a proteomic analysis of HPC secretome. Data show an enrichment in immune and TGF-beta regulators, ECM components and remodeling proteins in HPC secretome. Consistently, HPC-derived conditioned medium promotes hepatic stellate cell (HSC) activation and macrophage M1-like polarization. Strikingly, EGF and bile acids co-treatment leads to profound changes in the secretome composition, illustrated by an abolishment of HSC activating effect and by promoting macrophage M2-like polarization. Collectively, we provide new specific mechanisms behind HPC regulatory action during cholestatic liver injury, with an active role in cellular interactome and inflammatory response regulation. Moreover, findings prove a key contribution for EGFR signaling jointly with bile acids in HPC-mediated actions

Boosting NAD preferentially blunts Th17 inflammation via arginine biosynthesis and redox control in healthy and psoriasis subjects

Acknowledgments We thank Myron Waclawiw of the NHLBI Biostatistics Branch for assistance with the clinical protocol design, Chromadex for supplying NR and matching placebo capsules for the in vivo study and NR powder for the cell culture studies, and an NIH Bench-to-Bedside award for supplemental funding. We additionally thank Dr. Nina Klimova, formerly of the NHLBI, and Dr. Yun-Wei A. Hsu for their support of the metabolomics analysis at the Northwest Metabolomics Research Center of the University of Washington (NIH grant 1S10OD021562-01). We thank and acknowledge the assistance of the NHLBI DNA Sequencing and Genomics Core in performing the RNA library sequencing and Dr. Pradeep Dagur in the NHLBI Flow Cytometry Core for performing the immunophenotyping. Trial registration was as follows: ClinicalTrials.gov: NCT01934660, NCT02812238, and NCT01143454 and NIH Clinical Center blood bank (ClinicalTrials.gov: NCT00001846). This work was supported by the NHLBI Division of Intramural Research (ZIA-HL005102 to M.N.S.), NIH Bench-to-Bedside award (HL-129510-04S1 to M.N.S. and R.T.) and the NIH Office of Dietary Supplements (J.T.), the Spanish Ministry of Science and Innovation (RYC2018-026050-I and PID2019-105665RA-I00 to J.T.), and the UK MRC (MR/P011705/2 and UKDRI-5002 to J.L.G.; MAP UK).Peer reviewedPublisher PD

11th International Conference on Practical Applications of Agents and Multi-Agent Systems

Research on Agents and Multi-agent Systems has matured during the last decade and many effective applications of this technology are now deployed. PAAMS provides an international forum to presents and discuss the latest scientific developments and their effective applications, to assess the impact of the approach, and to facilitate technology transfer. PAAMS started as a local initiative, but since grown to become the international yearly platform to present, to discuss, and to disseminate the latest developments and the most important outcomes related to real-world applications. It provides a unique opportunity to bring multi-disciplinary experts, academics and practitioners together to Exchange their experience in the development and deployment of Agents and Multiagents systems. PAAMS intends to bring together researchers and developers from industry and the academic world to report on the latest scientific and technical advances on the application of multi-agent systems, to discuss and debate the major issues, and to showcase the latest systems using agent based technology. It will promote a forum for discussion on how agent based techniques, methods and tools help system designers to accomplish the mapping between available agent technology and application needs. Other stakeholders should be rewarded with a better understanding of the potential and challenges of the agent-oriented approach. This edition of PAAMS special sessions is organized by the Bioinformatics, Intelligent System and Educational Technology Research Group (http://bisite.usal.es) of the University of Salamanca. The present edition was held in Salamanca, Spain, from 22nd to 24th May 2013