OPA1 belongs to the Dynamin large GTPase protein family. OPA1 exists as a single-pass membrane protein localized in the mitochondrial inner membrane and also as a soluble form in the mitochondrial intermembrane space. There, it is a key player in fusion of the inner mitochondrial membrane as well as maintenance of the cristae architecture. The oligomerization of differentially processed forms of OPA1 directs mitochondrial membrane formation. It is expressed in brain, retina, testis, heart, and skeletal muscle. In response to intrinsic apoptotic signals, OPA1 proteolytic processing may lead to disassembly of the oligomers, allowing release of caspase activator Cytochrome C into the intermembrane space. The OPA1 form S1 is its inactive form resulting by cleavage by the OMA1 enzyme at S1 position. The cleavage occurs in response to stress conditions that induce the loss of mitochondrial membrane potential, ultimately resulting in decreased mitochondrial fusion. OPA1 defects have been linked to dominant optic atrophy plus syndrome (DOA+) and optic atrophy 1, a dominantly inherited optic neuropathy causing vision loss.
Johnson, et al. used the OPA1 antibody in their fission and fusion studies into mitochondrial morphology (1). Their immunoblotting with OPA1 antibody provided new insight into the pathophysiology of perturbed acid-base transporters and pH homeostasis found in membrane fusion-deficient mutants in mammalian cell culture and C. elegans systems. Thrombin medicates the shedding of an N-terminal fragment of tumor endothelial marker 5 (TEM5) and expression studies with OPA1 antibody and the cell-surface protein disulfide-isomerase (PDI) suggest that PDI exerts its actions by reducing crucial disulfide bonds within TEM5, which has important implications for angiogenesis and cell adhesion (2). Dai’s group has interestingly found that scavenging mitochondrial reactive oxygen species (ROS) induces a unique subset of alterations in the proteome as the OPA1 antibody was to help analyze a pressure overload-induced heart failure model in mice (3). Ussakli’s group performed expression profiling using the OPA1 antibody to characterize alterations found in ulcerative colitis (UC), and found that UC exhibits a bimodal pattern of mitochondrial loss and gain of function that may be useful in understanding tumor progression (4).
Novus Biologicals offers OPA1 reagents for your research needs including: