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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
Mutations in DNM1L, as in OPA1, result indominant optic atrophy despite opposite effectson mitochondrial fusion and fission
Brain, Volume 140, No. 10, Year 2017
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Description
Dominant optic atrophy is a blinding disease due to the degeneration of the retinal ganglion cells, the axons of which form the optic nerves. In most cases, the disease is caused by mutations in OPA1, a gene encoding a mitochondrial large GTPase involved in cristae structure and mitochondrial network fusion. Using exome sequencing, we identified dominant mutations in DNM1L on chromosome 12p11.21 in three large families with isolated optic atrophy, including the two families that defined the OPA5 locus on chromosome 19q12.1-13.1, the existence of which is denied by the present study. Analyses of patient fibroblasts revealed physiological abundance and homo-polymerization of DNM1L, forming aggregates in the cytoplasm and on highly tubulated mitochondrial network, whereas neither structural difference of the peroxisome network, nor alteration of the respiratory machinery was noticed. Fluorescence microscopy of wild-type mouse retina disclosed a strong DNM1L expression in the ganglion cell layer and axons, and comparison between 3-month-old wild-type and Dnm1l+ / mice revealed increased mitochondrial length in retinal ganglion cell soma and axon, but no degeneration. Thus, our results disclose that in addition to OPA1, OPA3, MFN2, AFG3L2 and SPG7, dominant mutations in DNM1L jeopardize the integrity of the optic nerve, suggesting that alterations of the opposing forces governing mitochondrial fusion and fission, similarly affect retinal ganglion cell survival. © The Author (2017).
Authors & Co-Authors
Gerber, Sylvie
France, Paris
Inserm
Charif, Majida
France, Angers
Biologie Neurovasculaire et Mitochondriale Intégrée
Chevrollier, Arnaud
France, Angers
Biologie Neurovasculaire et Mitochondriale Intégrée
Angebault, Claire
France, Montpellier
Institut Des Neurosciences de Montpellier
Kane, Mariame Selma
France, Angers
Biologie Neurovasculaire et Mitochondriale Intégrée
Alban, Jennifer
France, Angers
Biologie Neurovasculaire et Mitochondriale Intégrée
Quilès, Mélanie
France, Montpellier
Institut Des Neurosciences de Montpellier
Delettre, Cécile
France, Montpellier
Institut Des Neurosciences de Montpellier
Bonneau, Dominique
France, Angers
Biologie Neurovasculaire et Mitochondriale Intégrée
Procaccio, Vincent
France, Angers
Biologie Neurovasculaire et Mitochondriale Intégrée
Amati-Bonneau, Patrizia
France, Angers
Biologie Neurovasculaire et Mitochondriale Intégrée
Reynier, Pascal
France, Angers
Biologie Neurovasculaire et Mitochondriale Intégrée
Leruez, Stéphanie
France, Angers
Biologie Neurovasculaire et Mitochondriale Intégrée
Boddaert, Nathalie
France, Paris
Université Paris Cité
France, Creteil
Hôpital Henri Mondor
Funalot, Benoi̧t
France, Paris
Université Paris Cité
France, Creteil
Hôpital Henri Mondor
Rio, Marlène
France, Paris
Université Paris Cité
France, Creteil
Hôpital Henri Mondor
Bouccara, Didier
France, Paris
Hôpital Universitaire Pitié Salpêtrière
Meunier, Isabelle Anne
France, Montpellier
Institut Des Neurosciences de Montpellier
Kaplan, Josseline C.
France, Paris
Inserm
Hamel, Christian P.
France, Montpellier
Institut Des Neurosciences de Montpellier
Rozet, Jean Michel
France, Paris
Inserm
Lenaers, Guy
France, Angers
Biologie Neurovasculaire et Mitochondriale Intégrée
Statistics
Citations: 92
Authors: 22
Affiliations: 8
Identifiers
Doi:
10.1093/brain/awx219
ISSN:
00068950
Research Areas
Genetics And Genomics
Health System And Policy