Optic atrophy 1 (OPA1)

Optic atrophy 1 (OPA1) is a nuclear-encoded mitochondrial dynamin-like GTPase, primarily localized to the inner mitochondrial membrane. OPA1 is a key regulator of mitochondrial fusion, cristae architecture, oxidative phosphorylation, and apoptosis. It exists as multiple isoforms generated by alternative splicing, including long (L-OPA1) and short (S-OPA1) forms, which together mediate mitochondrial dynamics and network integrity. OPA1 dysfunction leads to misshapen, fragmented, and dysfunctional mitochondria, especially in cells with high energy demands such as retinal ganglion cells. Mutations in OPA1 are the most common cause of autosomal dominant optic atrophy, a progressive optic neuropathy characterized by childhood-onset vision loss, and can also give rise to more severe syndromes with extraocular manifestations. OPA1 is also implicated in neuronal maturation and synaptic development, indicating broader roles in neurodevelopment and metabolism. Recently, OPA1 was found to regulate lipolysis in adipocytes, expanding its functional repertoire beyond mitochondrial dynamics. Therapeutic strategies are focused on increasing functional OPA1 protein to rescue mitochondrial dysfunction and prevent neurodegeneration, with investigational agents like STK-002 currently under evaluation.

Other names

Dynamin-like 120 kDa protein, mitochondrialDynamin-like protein OPA1Mitochondrial dynamin-like GTPase OPA1

Increasing OPA1 protein levels by reducing poison exon inclusion (STK-002); No FDA-approved drugs targeting OPA1 currently exist