Human erythroid differentiation requires VDAC1-mediated mitochondrial clearance

Erythroblast maturation in mammals is dependent on organelle clearance throughout terminal erythropoiesis. We studied the role of the outer mitochondrial membrane protein voltage-dependent anion channel-1 (VDAC1) in human terminal erythropoiesis. We show that short hairpin (shRNA)-mediated downregulation of VDAC1 accelerates erythroblast maturation. Thereafter, erythroblasts are blocked at the orthochromatic stage, exhibiting a significant decreased level of enucleation, concomitant with an increased cell death. We demonstrate that mitochondria clearance starts at the transition from basophilic to polychromatic erythroblast, and that VDAC1 downregulation induces the mitochondrial retention. In damaged mitochondria from non-erythroid cells, VDAC1 was identified as a target for Parkin-mediated ubiquitination to recruit the phagophore. Here, we showed that VDAC1 is involved in phagophore’s membrane recruitment regulating selective mitophagy of still functional mitochondria from human erythroblasts. These findings demonstrate for the first time a crucial role for VDAC1 in human erythroblast terminal differentiation, regulating mitochondria clearance.Fil: Moras, Martina. Universite de Paris; Francia. Institut National de Transfusion Sanguine; Francia. Laboratoire d’Excellence GR-Ex; FranciaFil: Hattab, Claude. Universite de Paris; Francia. Institut National de Transfusion Sanguine; Francia. Laboratoire d’Excellence GR-Ex; FranciaFil: Gonzalez Menendez, Pedro. Laboratoire d’Excellence GR-Ex; Francia. Université Montpellier II; Francia. Centre National de la Recherche Scientifique; FranciaFil: Fader Kaiser, Claudio Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; Argentina. Universidad Nacional de Cuyo. Facultad de Odontologia; ArgentinaFil: Dussiot, Michael. Universite de Paris; Francia. Laboratoire d’Excellence GR-Ex; FranciaFil: Larghero, Jerome. Hôpital Saint-Louis. Unité de Thérapie cellulaire; FranciaFil: Le Van Kim, Caroline. Universite de Paris; Francia. Institut National de Transfusion Sanguine; Francia. Laboratoire d’Excellence GR-Ex; FranciaFil: Kinet, Sandrina. Laboratoire d’Excellence GR-Ex; Francia. Université Montpellier II; Francia. Centre National de la Recherche Scientifique; FranciaFil: Taylor, Naomi. Laboratoire d’Excellence GR-Ex; Francia. Centre National de la Recherche Scientifique; Francia. Université Montpellier II; Francia. Center for Cancer Research; Estados UnidosFil: Lefevre, Sophie D.. Universite de Paris; Francia. Institut National de Transfusion Sanguine; Francia. Laboratoire d’Excellence GR-Ex; FranciaFil: Ostuni, Mariano. Universite de Paris; Francia. Institut National de Transfusion Sanguine; Francia. Laboratoire d’Excellence GR-Ex; Franci

TSPO ligands stimulate ZnPPIX transport and ROS accumulation leading to the inhibition of P. falciparum growth in human blood

After invading red blood cells (RBCs), Plasmodium falciparum (Pf) can export its own proteins to the host membrane and activate endogenous channels that are present in the membrane of RBCs. This transport pathway involves the Voltage Dependent Anion Channel (VDAC). Moreover, ligands of the VDAC partner TranSlocator PrOtein (TSPO) were demonstrated to inhibit the growth of the parasite. We studied the expression of TSPO and VDAC isoforms in late erythroid precursors, examined the presence of these proteins in membranes of non-infected and infected human RBCs, and evaluated the efficiency of TSPO ligands in inhibiting plasmodium growth, transporting the haem analogue Zn-protoporphyrin-IX (ZnPPIX) and enhancing the accumulation of reactive oxygen species (ROS). TSPO and VDAC isoforms are differentially expressed on erythroid cells in late differentiation states. TSPO2 and VDAC are present in the membranes of mature RBCs in a unique protein complex that changes the affinity of TSPO ligands after Pf infection. TSPO ligands dose-dependently inhibited parasite growth, and this inhibition was correlated to ZnPPIX uptake and ROS accumulation in the infected RBCs. Our results demonstrate that TSPO ligands can induce Pf death by increasing the uptake of porphyrins through a TSPO2-VDAC complex, which leads to an accumulation of ROS

An open-source framework to model present and future marine species distributions at local scale

(IF 3.14; Q2)International audienceSpecies Distribution Models (SDMs) are useful tools to project potential future species distributions under climate change scenarios. Despite the ability to run SDMs in recent and reliable tools, there are some misuses and proxies that are widely practiced and rarely addressed together, particularly when dealing with marine species.In this paper, we propose an open-source framework that includes (i) a procedure for homogenizing occurrence data to reduce the influence of sampling bias, (ii) a procedure for generating pseudo-absences, (iii) a hierarchical-filter approach, (iv) full incorporation of the third dimension by considering climatic variables at multiple depths and (v) building of maps that predict current and potential future ranges of marine species. This framework is available for non-modeller ecologists interested in investigating future species ranges with a user-friendly script. We investigated the robustness of the framework by applying it to marine species of the Eastern English Channel. Projections were built for the middle and the end of this century under RCP2.6 and RCP8.5 scenarios

Toward an ecosystem approach of Marine Renewable Energy: the case of the offshore wind farm of Courseulles-sur-mer in the Bay of Seine

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Toward an ecosystem approach of Marine Renewable Energy: the case of the offshore wind farm of Courseulles-sur-mer in the Bay of Seine

International audienc

Effets cumulés des énergies marines renouvelables et du changement climatique sur les propriétés des écosystèmes : Sensibilité de l'analyse des réseaux écologiques

International audienceIn an increasingly anthropogenic world, the scientific community and managers have to take interactions between the drivers of ecosystems into consideration. Tools like ecological network analysis (ENA) indices offer the opportunity to study those interactions at the ecosystem level. However, ENA indices have never been used to test the incidence of cumulative drivers. The present study uses models combining the effects of (i) the reef caused by the future offshore wind farm of Courseulles-sur-Mer and (ii) climate change on species distribution, to test the response of multiple ENA indices. ENA indices proved sensitive to this cumulative impact, displaying a wide variety of cumulative effects. They were also very powerful to characterize the role of the cumulative impact on ecosystem functioning. These results demonstrate the capacity of ENA indices to describe and understand cumulative effects at the ecosystem scale. Using a sensitivity analysis approach, this study shows that ENA indices could be viable tools for managers. To help them in their tasks, the next step could be to link ecosystem services to ENA indices for a more practical use

Homeostasis of extracellular ATP in uninfected RBCs from a Plasmodium falciparum culture and derived microparticles

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