title: Standardized mitochondrial analysis gives new insights into mitochondrial dynamics and OPA1 function.
abstract: Mitochondria form dynamic tubular networks through processes of fission and fusion. Defect in mitochondrial dynamics lead to various pathologies, including several common and some rare neurodegenerative disorders. OPA1 and MFN2 are two key players in mitochondrial fusion associated with Autosomal Dominant Optic Atrophy and Charcot Marie Tooth neuropathy type 2A respectively. We used micropatterned coverslips to standardize the visualization of mitochondrial distribution in skin fibroblasts. In fibroblasts from affected patients, mutations in the OPA1 and MFN2 genes were found to affect the volume and cellular distribution of mitochondria. In G1/S cell cycle phase, mitochondria emerging from the microtubule organizing centre may be crucial to mitochondrial biogenesis since it appeared to be protected against mitochondrial fragmentation induced by OPA1 mutations. The standardized quantitative analysis of the mitochondrial network and the description of mitochondrial subcellular distribution should lead to better diagnostic criteria for mitochondrial diseases and yield new insights into mitochondrial dysfunction in disease and aging.
authors.affiliation: CNRS 6214, Angers F-49000, France. archevrollier@chu-angers.fr
authors.forename: Arnaud
authors.initials: A
authors.lastname: Chevrollier
authors.forename: Julien
authors.initials: J
authors.lastname: Cassereau
authors.forename: Marc
authors.initials: M
authors.lastname: Ferré
authors.forename: Jennifer
authors.initials: J
authors.lastname: Alban
authors.forename: Valérie
authors.initials: V
authors.lastname: Desquiret-Dumas
authors.forename: Naïg
authors.initials: N
authors.lastname: Gueguen
authors.forename: Patrizia
authors.initials: P
authors.lastname: Amati-Bonneau
authors.forename: Vincent
authors.initials: V
authors.lastname: Procaccio
authors.forename: Dominique
authors.initials: D
authors.lastname: Bonneau
authors.forename: Pascal
authors.initials: P
authors.lastname: Reynier
mesh_terms: D001483:Base Sequence; D005260:Female; D020558:GTP Phosphohydrolases / Q000235:genetics / Q000502:physiology*; D006801:Humans; D008297:Male; D008928:Mitochondria / Q000378:metabolism / Q000502:physiology*; D009154:Mutation; D034741:RNA, Small Interfering
chemical_list: D034741:RNA, Small Interfering; D020558:GTP Phosphohydrolases; C415198:OPA1 protein, human