OPA1

The protein encoded by this gene is a nuclear-encoded mitochondrial protein with similarity to dynamin-related GTPases. The encoded protein localizes to the inner mitochondrial membrane and helps regulate mitochondrial stability and energy output. This protein also sequesters cytochrome c. Mutations in this gene have been associated with optic atrophy type 1, which is a dominantly inherited optic neuropathy resulting in progressive loss of visual acuity, leading in many cases to legal blindness. [provided by RefSeq, Aug 2017]

OPA1, Mitochondrial Dynamin Like GTPase

Dynamin-related GTPase that is essential for normal mitochondrial morphology by regulating the equilibrium between mitochondrial fusion and mitochondrial fission (PubMed:16778770, PubMed:17709429, PubMed:20185555, PubMed:24616225, PubMed:28746876).
Coexpression of isoform 1 with shorter alternative products is required for optimal activity in promoting mitochondrial fusion (PubMed:17709429).
Binds lipid membranes enriched in negatively charged phospholipids, such as cardiolipin, and promotes membrane tubulation (PubMed:20185555).
The intrinsic GTPase activity is low, and is strongly increased by interaction with lipid membranes (PubMed:20185555).
Plays a role in remodeling cristae and the release of cytochrome c during apoptosis (By similarity).
Proteolytic processing in response to intrinsic apoptotic signals may lead to disassembly of OPA1 oligomers and release of the caspase activator cytochrome C (CYCS) into the mitochondrial intermembrane space (By similarity).
Plays a role in mitochondrial genome maintenance (PubMed:20974897, PubMed:18158317).
Dynamin-like 120 kDa protein, form S1
Inactive form produced by cleavage at S1 position by OMA1 following stress conditions that induce loss of mitochondrial membrane potential, leading to negative regulation of mitochondrial fusion.
Isoforms that contain the alternative exon 4b (present in isoform 4 and isoform 5) are required for mitochondrial genome maintenance, possibly by anchoring the mitochondrial nucleoids to the inner mitochondrial membrane.

Apoptotic processIEA:UniProtKB-KW
Axonal transport of mitochondrionManual Assertion Based On ExperimentTAS:UniProtKB
Cellular senescenceManual Assertion Based On ExperimentIDA:UniProtKB
GTP metabolic processManual Assertion Based On ExperimentIDA:UniProtKB
Inner mitochondrial membrane organizationManual Assertion Based On ExperimentIDA:UniProtKB
Membrane tubulationManual Assertion Based On ExperimentIDA:UniProtKB
Mitochondrial fissionManual Assertion Based On ExperimentTAS:UniProtKB
Mitochondrial fusionManual Assertion Based On ExperimentIDA:UniProtKB
Mitochondrial genome maintenanceManual Assertion Based On ExperimentIMP:UniProtKB
Mitochondrion organizationManual Assertion Based On ExperimentIMP:MGI
Negative regulation of apoptotic processManual Assertion Based On ExperimentIDA:UniProtKB
Negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathwayManual Assertion Based On ExperimentIGI:ParkinsonsUK-UCL
Negative regulation of release of cytochrome c from mitochondriaManual Assertion Based On ExperimentIMP:UniProtKB
Neural tube closureIEA:Ensembl
Protein complex oligomerizationManual Assertion Based On ExperimentIDA:UniProtKB
Visual perceptionManual Assertion Based On ExperimentIMP:UniProtKB

Mitochondrion inner membrane
Mitochondrion intermembrane space
Mitochondrion membrane
Detected at contact sites between endoplasmic reticulum and mitochondrion membranes.

Optic atrophy 1 (OPA1):
A condition that features progressive visual loss in association with optic atrophy. Atrophy of the optic disk indicates a deficiency in the number of nerve fibers which arise in the retina and converge to form the optic disk, optic nerve, optic chiasm and optic tracts. OPA1 is characterized by an insidious onset of visual impairment in early childhood with moderate to severe loss of visual acuity, temporal optic disk pallor, color vision deficits, and centrocecal scotoma of variable density.
Dominant optic atrophy plus syndrome (DOA+):
A neurologic disorder characterized most commonly by an insidious onset of visual loss and sensorineural hearing loss in childhood with variable presentation of other clinical manifestations including progressive external ophthalmoplegia, muscle cramps, hyperreflexia, and ataxia. There appears to be a wide range of intermediate phenotypes.
Behr syndrome (BEHRS):
An autosomal recessive syndrome characterized by optic atrophy beginning in early childhood associated with ataxia, pyramidal signs, spasticity, mental retardation, and posterior column sensory loss. The ataxia, spasticity, and muscle contractures, mainly of the hip adductors, hamstrings, and soleus, are progressive and become more prominent in the second decade.
Mitochondrial DNA depletion syndrome 14, cardioencephalomyopathic type (MTDPS14):
An autosomal recessive mitochondrial disorder characterized by lethal infantile encephalopathy, hypertrophic cardiomyopathy and optic atrophy. Skeletal muscle biopsies show significant mtDNA depletion and abnormal mitochondria.

Mitochondrial matrix: 88-96
Helical: 97-113
Mitochondrial intermembrane: 114-960

PARL-dependent proteolytic processing releases an antiapoptotic soluble form not required for mitochondrial fusion. Cleaved by OMA1 at position S1 following stress conditions.
Isoform 2
Cleavage at position S2 is mediated by YME1L (PubMed:17709429, PubMed:24616225, PubMed:27495975).
Cleavage may occur in the sequence motif Leu-Gln-Gln-Gln-Ile-Gln (LQQQIQ) (PubMed:16778770).
Isoform 3
Cleavage at position S2 is mediated by YME1L (PubMed:17709429, PubMed:24616225, PubMed:27495975).
Cleavage may occur in the sequence motif Leu-Gln-Gln-Gln-Ile-Gln (LQQQIQ) (PubMed:16778770).
Isoform 4
Cleavage at position S2 is mediated by YME1L (PubMed:17709429, PubMed:24616225, PubMed:27495975).
Cleavage may occur in the sequence motif Leu-Gln-Gln-Gln-Ile-Gln (LQQQIQ) (PubMed:16778770).