OPA1 mitochondrial dynamin-like GTPase (OPA1)

OPA1 mitochondrial dynamin-like GTPase (OPA1) is a nuclear-encoded, dynamin-related large GTPase localized to the mitochondrial inner membrane that is essential for mitochondrial inner-membrane fusion and cristae organization.[7][3] The human OPA1 gene produces at least eight splice variants; mitochondrial processing generates long, membrane-anchored L-OPA1 isoforms that are fusion-competent and short, intermembrane-space S-OPA1 isoforms that are fusion-inactive, through cleavage by OMA1 and YME1L at defined S1/S2 sites.[3][4][1] OPA1 supports mitochondrial energetics by stabilizing cristae, promoting ATP synthase dimerization, maintaining mtDNA, and limiting cytochrome c release and apoptosis under stress.[3][5][2] Pathogenic variants in OPA1 cause autosomal dominant optic atrophy, often starting in childhood, and may present with syndromic features including sensorineural hearing loss and mitochondrial myopathy.[5][2] Therapeutic efforts include splice-switching antisense oligonucleotides (e.g., STK-002) to increase OPA1 protein levels for DOA.[2]

Other names

Optic atrophy 1 protein (Optic atrophy-1)Dynamin-like 120 kDa proteinOPA1, mitochondrialGTPase OPA1

Splice-switching antisense oligonucleotide (e.g., STK-002) reduces poison exon inclusion in OPA1 mRNA to increase OPA1 protein, aiming to restore fusion/cristae integrity and retinal ganglion cell survival in DOA Indirect modulators: mitochondrial depolarizers or OXPHOS inhibitors trigger OMA1/YME1L cleavage of OPA1, shifting long fusion-competent forms (L-OPA1) to short forms (S-OPA1) and inhibiting fusion; these are mechanistic tools rather than therapies