Dominant mutations in MIEF1 affect mitochondrial dynamics and cause a singular late onset optic neuropathy
| Autor: | Dominique Bonneau, Agnès Guichet, Philippe Bensaid, Catherine Vignal, Patrizia Amati-Bonneau, Majida Charif, Soojin Kim, Yvette C. Wong, Pascal Reynier, Dimitri Krainc, Guy Lenaers, Vincent Procaccio, Xavier Zanlonghi |
|---|---|
| Přispěvatelé: | MitoVasc - Physiopathologie Cardiovasculaire et Mitochondriale (MITOVASC), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), University of Mohammed I - Université Mohammed Premier, Northwestern University Feinberg School of Medicine, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Fondation Ophtalmologique Adolphe de Rothschild [Paris], Clinique Jules Verne, LENAERS, Guy |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Retinal Ganglion Cells
0301 basic medicine Mitochondrial disease Mitochondria dynamics Mitochondrial disease MIEF1 Mid51 Dominant optic atrophy (DOA) Inherited optic neuropathy (ION) Peripheral visual field Neurodegeneration [SDV]Life Sciences [q-bio] Short Report Mid51 Cellular homeostasis Biology lcsh:Geriatrics Mitochondrial Dynamics Retinal ganglion lcsh:RC346-429 Mitochondrial Proteins Optic neuropathy 03 medical and health sciences Cellular and Molecular Neuroscience 0302 clinical medicine Optic Nerve Diseases medicine Humans Inherited optic neuropathy (ION) Neurodegeneration Molecular Biology lcsh:Neurology. Diseases of the nervous system Peripheral visual field MIEF1 Membrane Proteins Signal transducing adaptor protein Mitochondria dynamics Peptide Elongation Factors medicine.disease Eukaryotic translation elongation factor 1 alpha 1 Mitochondria Cell biology [SDV] Life Sciences [q-bio] lcsh:RC952-954.6 030104 developmental biology Mitochondrial fission Neurology (clinical) 030217 neurology & neurosurgery Dominant optic atrophy (DOA) |
| Zdroj: | Molecular Neurodegeneration, Vol 16, Iss 1, Pp 1-9 (2021) Molecular Neurodegeneration Molecular Neurodegeneration, 2021, 16 (1), pp.12. ⟨10.1186/s13024-021-00431-w⟩ |
| ISSN: | 1750-1326 |
| DOI: | 10.1186/s13024-021-00431-w⟩ |
| Popis: | Inherited optic neuropathies are the most common mitochondrial diseases, leading to neurodegeneration involving the irreversible loss of retinal ganglion cells, optic nerve degeneration and central visual loss. Importantly, properly regulated mitochondrial dynamics are critical for maintaining cellular homeostasis, and are further regulated by MIEF1 (mitochondrial elongation factor 1) which encodes for MID51 (mitochondrial dynamics protein 51), an outer mitochondrial membrane protein that acts as an adaptor protein to regulate mitochondrial fission. However, dominant mutations in MIEF1 have not been previously linked to any human disease. Using targeted sequencing of genes involved in mitochondrial dynamics, we report the first heterozygous variants in MIEF1 linked to disease, which cause an unusual form of late-onset progressive optic neuropathy characterized by the initial loss of peripheral visual fields. Pathogenic MIEF1 variants linked to optic neuropathy do not disrupt MID51’s localization to the outer mitochondrial membrane or its oligomerization, but rather, significantly disrupt mitochondrial network dynamics compared to wild-type MID51 in high spatial and temporal resolution confocal microscopy live imaging studies. Together, our study identifies dominant MIEF1 mutations as a cause for optic neuropathy and further highlights the important role of properly regulated mitochondrial dynamics in neurodegeneration. |
| Databáze: | OpenAIRE |
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