Recombinant Human OPA1 protein

Specifications

Form

Liquid

General info

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 : 16778770, PubMed : 17709429, PubMed : 20185555, PubMed : 24616225, PubMed : 28628083, PubMed : 28746876, PubMed : 31922487, PubMed : 32228866, PubMed : 32567732, PubMed : 33130824, PubMed : 33237841, PubMed : 37612504, PubMed : 37612506). 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 : 31922487, PubMed : 32228866, PubMed : 33237841, PubMed : 37612504, PubMed : 37612506). Both forms (L-OPA1 and S-OPA1) cooperate to catalyze the fusion of the mitochondrial inner membrane (PubMed : 31922487, PubMed : 37612504, PubMed : 37612506). 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 : 20038677, PubMed : 31922487). The balance between L-OPA1 and S-OPA1 also influences cristae shape and morphology (By similarity). Involved in remodeling cristae and the release of cytochrome c during apoptosis (By similarity). 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 (By similarity). 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 (By similarity). Its role in mitochondrial morphology is required for mitochondrial genome maintenance (PubMed : 18158317, PubMed : 20974897).. Dynamin-like GTPase OPA1, long form. Constitutes the transmembrane long form (L-OPA1) that plays a central role in mitochondrial inner membrane fusion and cristae morphology (PubMed : 31922487, PubMed : 32228866, PubMed : 37612504, PubMed : 37612506). L-OPA1 and the soluble short form (S-OPA1) form higher-order helical assemblies that coordinate the fusion of mitochondrial inner membranes (PubMed : 31922487, PubMed : 37612504, PubMed : 37612506). 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 (PubMed : 37612504, PubMed : 37612506). Once at the membrane surface, the formation of S-OPA1 helices induce bilayer curvature (PubMed : 37612504, PubMed : 37612506). 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 (PubMed : 28628083, PubMed : 37612504, PubMed : 37612506). 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 : 32567732, PubMed : 33130824). 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 (By similarity).. Dynamin-like GTPase OPA1, short form. 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 : 31922487, PubMed : 32228866, PubMed : 32245890, PubMed : 37612504, PubMed : 37612506). The transmembrane long form (L-OPA1) and the S-OPA1 form higher-order helical assemblies that coordinate the fusion of mitochondrial inner membranes (PubMed : 31922487, PubMed : 32228866, PubMed : 37612504, PubMed : 37612506). 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 (PubMed : 32228866, PubMed : 37612504, PubMed : 37612506). Once at the membrane surface, the formation of S-OPA1 helices induce bilayer curvature (PubMed : 37612504, PubMed : 37612506). 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 (PubMed : 28628083, PubMed : 37612504, PubMed : 37612506). 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 : 20038677). 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 (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 : 32245890). 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 (By similarity).. Isoform 1. Coexpression of isoform 1 with shorter alternative products is required for optimal activity in promoting mitochondrial fusion.. Isoform 4. Isoforms that contain the alternative exon 4b are required for mitochondrial genome maintenance, possibly by anchoring the mitochondrial nucleoids to the inner mitochondrial membrane.. Isoform 5. Isoforms that contain the alternative exon 4b are required for mitochondrial genome maintenance, possibly by anchoring the mitochondrial nucleoids to the inner mitochondrial membrane.

Sequence similarities

Belongs to the TRAFAC class dynamin-like GTPase superfamily. Dynamin/Fzo/YdjA family.

Post-translational modifications

Cleaved by OMA1 or YME1L downstream of the transmembrane region in response to different signals to generate soluble forms (PubMed:16778770, PubMed:17709429, PubMed:20038677, PubMed:24616225, PubMed:27495975, PubMed:33237841). Cleaved by OMA1 at position S1 following stress conditions, generating the short soluble form (Dynamin-like GTPase OPA1, short form; S-OPA1) (PubMed:20038677). AFG3L2 is involved in the regulation of OMA1-dependent processing of OPA1 (PubMed:17615298). PARL-dependent proteolytic processing releases an antiapoptotic soluble form not required for mitochondrial fusion (By similarity).. Isoform 2. Cleavage at position S2 by YME1L is required to mediate oxidative phosphorylation (OXPHOS)-induced mitochondrial fusion (PubMed:17709429, PubMed:24616225, PubMed:27495975). Cleavage occurs in the sequence motif Leu-Gln-Gln-Gln-Ile-Gln (LQQQIQ) (PubMed:16778770).. Isoform 3. Cleavage at position S2 by YME1L is required to mediate oxidative phosphorylation (OXPHOS)-induced mitochondrial fusion (PubMed:17709429, PubMed:24616225, PubMed:27495975). Cleavage occurs in the sequence motif Leu-Gln-Gln-Gln-Ile-Gln (LQQQIQ) (PubMed:16778770).. Isoform 4. Cleavage at position S2 by YME1L is required to mediate oxidative phosphorylation (OXPHOS)-induced mitochondrial fusion (PubMed:17709429, PubMed:24616225, PubMed:27495975). Cleavage occurs in the sequence motif Leu-Gln-Gln-Gln-Ile-Gln (LQQQIQ) (PubMed:16778770). Cleavage at position S3 by YME1L is required for membrane tubulation (PubMed:33237841).. Isoform 5. Cleavage at position S3 by YME1L is required for membrane tubulation.

Subcellular localisation

Mitochondrion inner membrane