Dominant mutations in MIEF1 affect mitochondrial dynamics and cause a singular late onset optic neuropathy

Majida Charif, Yvette C. Wong, Soojin Kim, Agnès Guichet, Catherine Vignal, Xavier Zanlonghi, Philippe Bensaid, Vincent Procaccio, Dominique Bonneau, Patrizia Amati-Bonneau, Pascal Reynier, Dimitri Krainc, Guy Lenaers*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

14 Scopus citations


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.

Original languageEnglish (US)
Article number12
JournalMolecular neurodegeneration
Issue number1
StatePublished - Dec 2021


  • Dominant optic atrophy (DOA)
  • Inherited optic neuropathy (ION)
  • MIEF1
  • Mid51
  • Mitochondria dynamics
  • Mitochondrial disease
  • Neurodegeneration
  • Peripheral visual field

ASJC Scopus subject areas

  • Clinical Neurology
  • Cellular and Molecular Neuroscience
  • Molecular Biology


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