Contributors: Institut National de la Transfusion Sanguine Paris (INTS); Biologie Intégrée du Globule Rouge (BIGR (UMR_S_1134 / U1134)); Institut National de la Transfusion Sanguine Paris (INTS)-Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pointe-à-Pitre / Abymes Guadeloupe -Université des Antilles (UA)-Université Paris Cité (UPCité); Institut de Génétique Moléculaire de Montpellier (IGMM); Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS); Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163); Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité); Hopital Saint-Louis AP-HP (AP-HP); Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP); National Cancer Institute Bethesda (NCI-NIH); National Institutes of Health Bethesda, MD, USA (NIH); The authors would like to thank Mrs Corentine Chrysostome et Mr Abdellah Nait for their secretarial and technical assistance, respectively. We acknowledge the Cell Sorting facility of the Institut Imagine; the ImagoSeine core facility of the Institut Jacques Monod, member of IBiSA and France-BioImaging (ANR-10-INBS-04) infrastructure; the Laboratory of Excellence GR-Ex (Grant ANR-11-LABX-0051) and the Guests Researcher program from Paris Diderot University. Martina Moras is funded by the European Union’s Horizon 2020 2 research and innovation program under the Marie Skłodowska-Curie grant agreement No. 665850, the Club du Globule Rouge et du Fer (CGRF) and Société Française d’Hématologie (SFH). Pedro Gonzalez-Menendez is founded by the CLARIN-COFUND program from the Principado de Asturias and the European Union.; ANR-10-INBS-0004,France-BioImaging,Développment d'une infrastructure française distribuée coordonnée(2010); ANR-11-LABX-0051,GR-Ex,Biogenèse et pathologies du globule rouge(2011)
نبذة مختصرة : International audience ; Erythroblast maturation in mammals is dependent on organelle clearance throughout terminal erythropoiesis. We studied the role of the outer mitochondrial membrane protein VDAC1 (Voltage-Dependent Anion Channel-1) in human terminal erythropoiesis. We show that shRNA-mediated downregulation of VDAC1 accelerates erythroblast maturation. Thereafter, erythroblasts are blocked at 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.
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