Apolipoproteins L1 and L3 control mitochondrial membrane dynamics
Laurence Lecordier,
Paul Heo,
Jonas H. Graversen,
Dorle Hennig,
Maria Kløjgaard Skytthe,
Alexandre Cornet d’Elzius,
Frédéric Pincet,
David Pérez-Morga,
Etienne Pays
Affiliations
Laurence Lecordier
Laboratory of Molecular Parasitology, IBMM, Université Libre de Bruxelles, 6041 Gosselies, Belgium
Paul Heo
Laboratoire de Physique de l’Ecole Normale Supérieure, Ecole Normale Supérieure (ENS), Université Paris Sciences et Lettres (PSL), CNRS, Sorbonne Université, Université Paris-Cité, 75005 Paris, France; Institute of Psychiatry and Neuroscience of Paris, INSERM U1266, 75014 Paris, France
Jonas H. Graversen
Department of Molecular Medicine, Cancer and Inflammation Research, University of Southern Denmark, 5000 Odense C, Denmark
Dorle Hennig
Department of Molecular Medicine, Cancer and Inflammation Research, University of Southern Denmark, 5000 Odense C, Denmark
Maria Kløjgaard Skytthe
Department of Molecular Medicine, Cancer and Inflammation Research, University of Southern Denmark, 5000 Odense C, Denmark
Alexandre Cornet d’Elzius
Laboratory of Molecular Parasitology, IBMM, Université Libre de Bruxelles, 6041 Gosselies, Belgium
Frédéric Pincet
Laboratoire de Physique de l’Ecole Normale Supérieure, Ecole Normale Supérieure (ENS), Université Paris Sciences et Lettres (PSL), CNRS, Sorbonne Université, Université Paris-Cité, 75005 Paris, France
David Pérez-Morga
Laboratory of Molecular Parasitology, IBMM, Université Libre de Bruxelles, 6041 Gosselies, Belgium; Center for Microscopy and Molecular Imaging (CMMI), Université Libre de Bruxelles, 6041 Gosselies, Belgium
Etienne Pays
Laboratory of Molecular Parasitology, IBMM, Université Libre de Bruxelles, 6041 Gosselies, Belgium; Corresponding author
Summary: Apolipoproteins L1 and L3 (APOLs) are associated at the Golgi with the membrane fission factors phosphatidylinositol 4-kinase-IIIB (PI4KB) and non-muscular myosin 2A. Either APOL1 C-terminal truncation (APOL1Δ) or APOL3 deletion (APOL3-KO [knockout]) reduces PI4KB activity and triggers actomyosin reorganization. We report that APOL3, but not APOL1, controls PI4KB activity through interaction with PI4KB and neuronal calcium sensor-1 or calneuron-1. Both APOLs are present in Golgi-derived autophagy-related protein 9A vesicles, which are involved in PI4KB trafficking. Like APOL3-KO, APOL1Δ induces PI4KB dissociation from APOL3, linked to reduction of mitophagy flux and production of mitochondrial reactive oxygen species. APOL1 and APOL3, respectively, can interact with the mitophagy receptor prohibitin-2 and the mitophagosome membrane fusion factor vesicle-associated membrane protein-8 (VAMP8). While APOL1 conditions PI4KB and APOL3 involvement in mitochondrion fission and mitophagy, APOL3-VAMP8 interaction promotes fusion between mitophagosomal and endolysosomal membranes. We propose that APOL3 controls mitochondrial membrane dynamics through interactions with the fission factor PI4KB and the fusion factor VAMP8.
