UniprotKB/SwissProt ID: P58281 (P58281)
Gene Name:
Opa1
Organism: Mus musculus (Mouse)
Function: Dynamin-related GTPase that is essential for normal mitochondrial morphology by mediating fusion of the mitochondrial inner membranes, regulating cristae morphology and maintaining respiratory chain function (PubMed:11847212, PubMed:16839884, PubMed:16839885, PubMed:24055366, PubMed:24616225, PubMed:24627489, PubMed:25298396, PubMed:26785494, PubMed:28636943, PubMed:28746876, PubMed:33200421, PubMed:33237841, PubMed:36171294, PubMed:38225406). Exists in two forms: the transmembrane, long form (Dynamin-like GTPase OPA1, long form; L-OPA1), which is tethered to the inner mitochondrial membrane, and the short soluble form (Dynamin-like GTPase OPA1, short form; S-OPA1), which results from proteolytic cleavage and localizes in the intermembrane space (PubMed:24703695, PubMed:28636943, PubMed:33237841). Both forms (L-OPA1 and S-OPA1) cooperate to catalyze the fusion of the mitochondrial inner membrane (PubMed:33237841). The equilibrium between L-OPA1 and S-OPA1 is essential: excess levels of S-OPA1, produced by cleavage by OMA1 following loss of mitochondrial membrane potential, lead to an impaired equilibrium between L-OPA1 and S-OPA1, inhibiting mitochondrial fusion (PubMed:33200421). The balance between L-OPA1 and S-OPA1 also influences cristae shape and morphology (PubMed:33200421, PubMed:38225406). Involved in remodeling cristae and the release of cytochrome c during apoptosis (PubMed:16839884). Proteolytic processing by PARL 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 (PubMed:16839884, PubMed:16839885). Acts as a regulator of T-helper Th17 cells, which are characterized by cells with fused mitochondria with tight cristae, by mediating mitochondrial membrane remodeling: OPA1 is required for interleukin-17 (IL-17) production (PubMed:36171294). Its role in mitochondrial morphology is required for mitochondrial genome maintenance (By similarity) Constitutes the transmembrane long form (L-OPA1) that plays a central role in mitochondrial inner membrane fusion and cristae morphology (PubMed:20038678, PubMed:22433842, PubMed:25298396). L-OPA1 and the soluble short form (S-OPA1) form higher-order helical assemblies that coordinate the fusion of mitochondrial inner membranes (By similarity). Inner membrane-anchored L-OPA1 molecules initiate membrane remodeling by recruiting soluble S-OPA1 to rapidly polymerize into a flexible cylindrical scaffold encaging the mitochondrial inner membrane (By similarity). Once at the membrane surface, the formation of S-OPA1 helices induce bilayer curvature (By similarity). OPA1 dimerization through the paddle region, which inserts into cardiolipin-containing membrane, promotes GTP hydrolysis and the helical assembly of a flexible OPA1 lattice on the membrane, which drives membrane curvature and mitochondrial fusion (By similarity). Plays a role in the maintenance and remodeling of mitochondrial cristae, some invaginations of the mitochondrial inner membrane that provide an increase in the surface area (PubMed:16839884, PubMed:16839885, PubMed:25298396, PubMed:38225406). Probably acts by forming helical filaments at the inside of inner membrane tubes with the shape and dimensions of crista junctions (By similarity). The equilibrium between L-OPA1 and S-OPA1 influences cristae shape and morphology: increased L-OPA1 levels promote cristae stacking and elongated mitochondria, while increased S-OPA1 levels correlated with irregular cristae packing and round mitochondria shape (PubMed:38225406) Constitutes the soluble short form (S-OPA1) generated by cleavage by OMA1, which plays a central role in mitochondrial inner membrane fusion and cristae morphology (PubMed:20038678, PubMed:22433842, PubMed:25298396). The transmembrane long form (L-OPA1) and the S-OPA1 form higher-order helical assemblies that coordinate the fusion of mitochondrial inner membranes (By similarity). Inner membrane-anchored L-OPA1 molecules initiate membrane remodeling by recruiting soluble S-OPA1 to rapidly polymerize into a flexible cylindrical scaffold encaging the mitochondrial inner membrane (By similarity). Once at the membrane surface, the formation of S-OPA1 helices induce bilayer curvature (By similarity). OPA1 dimerization through the paddle region, which inserts into cardiolipin-containing membrane, promotes GTP hydrolysis and the helical assembly of a flexible OPA1 lattice on the membrane, which drives membrane curvature and mitochondrial fusion (By similarity). Excess levels of S-OPA1 produced by cleavage by OMA1 following stress conditions that induce loss of mitochondrial membrane potential, lead to an impaired equilibrium between L-OPA1 and S-OPA1, thereby inhibiting mitochondrial fusion (PubMed:20038678, PubMed:22433842). Involved in mitochondrial safeguard in response to transient mitochondrial membrane depolarization by mediating flickering: cleavage by OMA1 leads to excess production of S-OPA1, preventing mitochondrial hyperfusion (PubMed:24627489, PubMed:33200421). Plays a role in the maintenance and remodeling of mitochondrial cristae, some invaginations of the mitochondrial inner membrane that provide an increase in the surface area (PubMed:16839884, PubMed:16839885, PubMed:25298396, PubMed:38225406). Probably acts by forming helical filaments at the inside of inner membrane tubes with the shape and dimensions of crista junctions (By similarity). The equilibrium between L-OPA1 and S-OPA1 influences cristae shape and morphology: increased L-OPA1 levels promote cristae stacking and elongated mitochondria, while increased S-OPA1 levels correlated with irregular cristae packing and round mitochondria shape (PubMed:38225406) Isoforms that contain the alternative exon 4b are required for mitochondrial genome maintenance, possibly by anchoring the mitochondrial nucleoids to the inner mitochondrial membrane
Other Modifications: View all modification sites in dbPTM
Protein Subcellular Localization: Mitochondrion inner membrane. Mitochondrion intermembrane space
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