Dynamin-like 120 kDa mitochondrial protein (OPA1) (OPA1)

Dynamin-like 120 kDa mitochondrial protein (OPA1) is a nuclear-encoded GTPase localized to the inner mitochondrial membrane, where it is essential for maintaining mitochondrial integrity and function (UniProt P58281). Its primary biological roles include mediating mitochondrial inner membrane fusion, maintaining the structural integrity of mitochondrial cristae, and regulating apoptosis by controlling the release of cytochrome c (PubMed: 21549331). In the visual system, OPA1 is predominantly expressed in retinal ganglion cells (RGCs), which are highly susceptible to mitochondrial dysfunction due to their significant energy requirements and long axons (PubMed: 31434075). Mutations in the OPA1 gene are the most common cause of Autosomal Dominant Optic Atrophy (ADOA), leading to the progressive loss of RGCs and optic nerve degeneration (PubMed: 10932184). Therapeutic approaches currently in development, such as PYC-001 and STK-002, aim to address OPA1 haploinsufficiency by increasing protein expression through RNA-based technologies or gene supplementation (PubMed: 33513340). By restoring OPA1 levels, these treatments seek to stabilize mitochondrial networks, improve metabolic efficiency, and prevent the programmed cell death of RGCs. Beyond ADOA, OPA1 is also being investigated as a potential target for neuroprotection in glaucoma and other optic neuropathies.

Other names

Optic atrophy 1MGM1KIAA0453Large GTPase OPA1

Restoration of OPA1 protein levels to promote mitochondrial fusion and stabilize cristae, thereby preventing cytochrome c release and retinal ganglion cell apoptosis.