Optic atrophy 1 mitochondrial dynamin-like GTPase (OPA1) (OPA1)

Optic atrophy 1 mitochondrial dynamin-like GTPase (OPA1) is a nuclear-encoded protein localized to the inner mitochondrial membrane, where it plays a critical role in mitochondrial dynamics (UniProt P58281). It is primarily responsible for mediating the fusion of the inner mitochondrial membrane and maintaining the structural integrity of mitochondrial cristae (PubMed: 10932190). Beyond its structural roles, OPA1 is essential for sequestering cytochrome c within the cristae, thereby regulating the intrinsic apoptotic pathway (NCBI Gene: 4976). Mutations in the OPA1 gene are the leading cause of autosomal dominant optic atrophy (ADOA), a condition characterized by the progressive loss of retinal ganglion cells and optic nerve degeneration (StatPearls: NBK1478). In addition to ADOA, OPA1 dysfunction has been implicated in broader neurodegenerative processes, including Parkinson's and Alzheimer's diseases, due to its impact on mitochondrial DNA stability and oxidative phosphorylation (PubMed: 26073165). While there are currently no FDA-approved drugs that directly target OPA1, therapeutic strategies under investigation include gene therapies and antisense oligonucleotides like PYC-001 aimed at restoring OPA1 expression levels (PYC Therapeutics). Small molecule stabilizers such as MYLS22 are also being explored to enhance mitochondrial network balance in disease states (PubMed: 31919146).

Other names

Dynamin-like 120 kDa protein mitochondrialOptic atrophy 1 (autosomal dominant)KIAA0453MGM1

Upregulation of OPA1 protein expression or stabilization of mitochondrial inner membrane fusion and cristae structure.