Human erythroid differentiation requires VDAC1-mediated mitochondrial clearance
Martina Moras
(1, 2)
,
Claude Hattab
(1, 2)
,
Pedro Gonzalez-Menendez
(3)
,
Claudio Fader
,
Michael Dussiot
(4)
,
Jerome Larghero
(5)
,
Caroline Le van Kim
,
Sandrina Kinet
(3)
,
Naomi Taylor
(3, 6)
,
Sophie Lefevre
(1, 2)
,
Ma Ostuni
(1, 2)
1
INTS -
Institut National de la Transfusion Sanguine [Paris]
2 BIGR (UMR_S_1134 / U1134) - Biologie Intégrée du Globule Rouge
3 IGMM - Institut de Génétique Moléculaire de Montpellier
4 Imagine - U1163 - Imagine - Institut des maladies génétiques (IHU)
5 AP-HP - Hopital Saint-Louis [AP-HP]
6 NCI-NIH - National Cancer Institute [Bethesda]
2 BIGR (UMR_S_1134 / U1134) - Biologie Intégrée du Globule Rouge
3 IGMM - Institut de Génétique Moléculaire de Montpellier
4 Imagine - U1163 - Imagine - Institut des maladies génétiques (IHU)
5 AP-HP - Hopital Saint-Louis [AP-HP]
6 NCI-NIH - National Cancer Institute [Bethesda]
Claudio Fader
- Fonction : Auteur
Caroline Le van Kim
- Fonction : Auteur
- PersonId : 757928
- ORCID : 0000-0002-3251-1310
- IdRef : 113048041
Sandrina Kinet
- Fonction : Auteur
- PersonId : 740239
- IdHAL : sandrina-kinet
- ORCID : 0000-0003-0699-108X
- IdRef : 195695437
Naomi Taylor
- Fonction : Auteur
- PersonId : 857337
- ORCID : 0000-0002-2459-4558
- IdRef : 069480672
Sophie Lefevre
- Fonction : Auteur
- PersonId : 811845
- ORCID : 0000-0002-7504-1881
Ma Ostuni
- Fonction : Auteur
- PersonId : 16543
- IdHAL : mariano-ostuni
- ORCID : 0000-0001-6769-3786
- IdRef : 177420847
Résumé
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.
Domaines
Méthodes et statistiquesFormat du dépôt | Fichier |
---|---|
Type de dépôt | Article dans une revue |
Titre |
en
Human erythroid differentiation requires VDAC1-mediated mitochondrial clearance
|
Résumé |
en
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.
|
Auteur(s) |
Martina Moras
1, 2
, Claude Hattab
1, 2
, Pedro Gonzalez-Menendez
3
, Claudio Fader
, Michael Dussiot
4
, Jerome Larghero
5
, Caroline Le van Kim
, Sandrina Kinet
3
, Naomi Taylor
3, 6
, Sophie Lefevre
1, 2
, Ma Ostuni
1, 2
1
INTS -
Institut National de la Transfusion Sanguine [Paris]
( 266750 )
- 6 rue Alexandre Cabanel, 75739 Paris cedex 15
- France
2
BIGR (UMR_S_1134 / U1134) -
Biologie Intégrée du Globule Rouge
( 1005032 )
- 6 rue Alexandre Cabanel - 75739 Paris cedex 15
- France
3
IGMM -
Institut de Génétique Moléculaire de Montpellier
( 712 )
- 1919 Route de Mende - 34293 Montpellier Cedex 5
- France
4
Imagine - U1163 -
Imagine - Institut des maladies génétiques (IHU)
( 1004662 )
- IHU Imagine,
156 rue de Vaugirard, 75015 PARIS
et
24 Boulevard du Montparnasse, 75015 Paris
- France
5
AP-HP -
Hopital Saint-Louis [AP-HP]
( 506757 )
- 1 Avenue Claude Vellefaux, 75010 Paris
- France
6
NCI-NIH -
National Cancer Institute [Bethesda]
( 305678 )
- BG 9609 MSC 9760, 9609 Medical Center Drive, Bethesda, MD 20892-9760
- États-Unis
|
Langue du document |
Anglais
|
Nom de la revue |
|
Vulgarisation |
Non
|
Comité de lecture |
Oui
|
Audience |
Internationale
|
Date de publication |
2020-09-10
|
Projet(s) ANR |
|
Domaine(s) |
|
Financement |
|
DOI | 10.3324/haematol.2020.257121 |
PubMed Central | PMC8719069 |
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