OPA1 functions in mitochondria and dysfunctions in optic nerve.
OPA1 is the major gene responsible for Dominant Optic Atrophy (DOA), a blinding disease that affects specifically the retinal ganglion cells (RGCs), which function consists in connecting the neuro-retina to the brain. OPA1 encodes an intra-mitochondrial dynamin, involved in inner membrane structures and ubiquitously expressed, raising the critical question of the origin of the disease pathophysiology. Here, we review the fundamental knowledge on OPA1 functions and regulations, highlighting their involvements in mitochondrial respiration, membrane dynamic and apoptosis. In light of these functions, we then describe the remarkable RGC mitochondrial network physiology and analyse data collected from animal models expressing OPA1 mutations. If, to date RGC mitochondria does not present any peculiarity at the molecular level, they represent possible targets of numerous assaults, like light, pressure, oxidative stress and energetic impairment, which jeopardize their function and survival, as observed in OPA1 mouse models. Although fascinating fields of investigation are still to be addressed on OPA1 functions and on DOA pathophysiology, we have reached a conspicuous state of knowledge with pertinent cell and animal models, from which therapeutic trials can be initiated and deeply evaluated.
Lenaers
Guy
G
INSERM U-583, Institut des Neurosciences de Montpellier, Université de Montpellier I et II, Montpellier, France. guy.lenaers@inserm.fr
Reynier
Pascal
P
Elachouri
Ghizlane
G
Soukkarieh
Chadi
C
Olichon
Aurélien
A
Belenguer
Pascale
P
Baricault
Laurent
L
Ducommun
Bernard
B
Hamel
Christian
C
Delettre
Cécile
C
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D019069:Cell Respiration / Q000502:physiology; D020558:GTP Phosphohydrolases / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D008928:Mitochondria / Q000378:metabolism; D009900:Optic Nerve / Q000378:metabolism* / Q000473:pathology; D012165:Retinal Ganglion Cells / Q000378:metabolism / Q000473:pathology
D020558:GTP Phosphohydrolases