The following text describes a protein:
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 (By similarity). 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 (By similarity). Both forms (L-OPA1 and S-OPA1) cooperate to catalyze the fusion of the mitochondrial inner membrane (By similarity). 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 (By similarity). 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 (By similarity); [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 (By similarity). 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 (By similarity). 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 (By similarity). 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 (By similarity). 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 (By similarity). 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).
Subcellular Localization:
[Dynamin-like GTPase OPA1, long form]: Mitochondrion inner membrane; Single-pass membrane protein. Note=Detected at contact sites between endoplasmic reticulum and mitochondrion membranes; [Dynamin-like GTPase OPA1, short form]: Mitochondrion intermembrane space.
Domain:
The paddle region plays a major role in driving mitochondrial inner membrane fusion (By similarity). It binds lipid membranes enriched in negatively charged phospholipids, such as cardiolipin, and promotes membrane tubulation (By similarity). A conserved intramembrane region, named membrane insertion loop (MIL), within the paddle region inserts deeply into the bilayer, further stabilizing the interactions with cardiolipin-enriched membranes (By similarity). OPA1 dimerization through the paddle domain promotes the helical assembly of a flexible OPA1 lattice on the membrane, driving mitochondrial fusion in cells (By similarity).
Sequence:
MWRLRRAAVACEVCQSLVKHSSGIKGSLPLQKLHLVSRSIYHSHYPTLKLQRPQLRTSFQQFSSLTNLPLRKLKFSPIKYGYQPRRNFWPARLATRLLKLRYLILGSAVGGGYTAKKTFDQWKDMIPDLSEYKWIVPDIVWEIDEYIDFEKIRKALPNSEDLVKLAPDFDKIVESLSLLKDFFTSGSPGETAFRATDHGSESDKHFRKVSDKEKIDQLQEELLHTQLKYQRILERLEKENKELRKLVLQKDDKGIHHRKLKKSLIDMYSEVLDVLSDYDASYNTQDHLPRVVVVGDQSAGKTSVLEMIAQARIFPRGSGEMMTRSPVKVTLSEGPHHVALFKDSSREFDLTKEEDLAALRHEIELRMRKNVKEGCTVSPETISLNVKGPGLQRMVLVDLPGVINTVTSGMAPDTKETIFSISKAYMQNPNAIILCIQDGSVDAERSIVTDLVSQMDPHGRRTIFVLTKVDLAEKNVASPSRIQQIIEGKLFPMKALGYFAVVTGKGNSSESIEAIREYEEEFFQNSKLLKTSMLKAHQVTTRNLSLAVSDCFWKMVRESVEQQADSFKATRFNLETEWKNNYPRLRELDRNELFEKAKNEILDEVISLSQATPKHWEEILQQSLWERVSTHVIENIYLPAAQTMNSGTFNTTVDIKLKQWTDKQLPNKAVEVAWETLQGEFSRFMTEPKGKEHDDIFDKLKEAVKEESIKRHKWNDFAEDSLRVIQHNALEDRSISDKQQWDAAIYFMEEALQARLKDTENAIENMVGPDWKKRWLYWKNRTQEQCVHNETKNELEKMLKCNEEHPAYLASDEITTVRKNLESRGVEVDPSLIKDTWHQVYRRHFLKTALNHCNLCRRGFYYYQRHFVDSELECNDVVLFWRIQRMLAITANTLRQQLTNTEVRRLEKNVKEVLEDFAEDGEKKIKLLTGKRVQLAEDLKKVREIQEKLDAFIEALHQEK