Mitochondria are dynamic organelles that frequently move, divide, and fuse with one another to maintain their architecture and functions. Changes in mitochondrial morphology is tightly coupled with cell cycle, differentiation and death, these physiological phenomenon are regulated by the balance between mitochondrial fusion and fission process. Any disruption in dynamic equilibrium between fusion and fission due to cell injury or death may contribute to developmental and neurodegenerative disorders. Inhibition of fusion caused machinery can caused excessive fragmentation that led to dysfunctional organelle. Calcineurin dependent translocation of a pro-fission protein dynamin related protein 1 (Drp1) to mitochondria was observed in dysfunction-induced fragmentation. Drp1 interacts with cytosolic phosphatase calcineurin during mitochondrial depolarization due to sustained cytosolic Ca increase. The translocation of Drp1 is dependent upon calcineurin-dependent dephosphorylation of serine 637 of Drp1 (1). In neurons and in HeLa cells the CaMKI alfa-dependent phosphorylation of Ser600 by of Drp1 resulted in increased trans location of Drp1 in to mitochondria (2).
Fragmentation of mitochondria triggered by dysfunction of the Drp1 protein led to synaptic damage and subsequent neuronal loss and impaired bioenergetics. Excessive fragmentation results in abnormally small mitochondria with broken cristae as observed in electron microscopy of neurons from studies of Alzheimer’s disease (3). Recent studies have suggested that Drp1 undergo S-Nitrosylation which regulate its activity to induce mitochondrial fission and neuronal damage in a NO mediated fashion (4). It is suggested that NO produced in response to beta-amyloid protein play a key role in mitochondrial fission, synaptic loss and neuronal damage in Alzheimer disease via S-notrosylation of Drp1 forming SNO-Drp1 (4). Increased concentration of SNO-Drp1 is found in Alzheimer’s brain which may contribute to the pathogenesis of neuro-degeneration. Preventing nitrosolyation of Drp1 abrogates the neurotoxic events. Drp1 (736 aa) is a highly conserved protein among humans, rat, mouse and fly genome. The protein has a amino terminal Ras-like GTPase superfamily domain, a Dynamin-M domain and a GED domain.
FabGennix has made and characterized an antibody against Dynamin-related protein 1 (Dlr1) in rabbit, this antibody cross reacts with mouse, rat, human and fruit fly Drp1 protein. The Drp1antibodies are affinity purified over immobilized antigen affinity matrix and stabilized in the presence of preservatives for long-term storage. FITC-Drp1 conjugated antibody was further purified to remove un-conjugated fluorophore was stabilized for long-term storage. FabGennix will conjugate this antibody to secondary enzymes (alkaline phosphatase or horseradish peroxidase) and other fluorophores upon request at a nominal charge. FabGennix Int. Inc. stocks limited quantities of western blot positive controls for Drp1 in ready-to-use buffers and antigenic blocking protein/peptide for immuno-depletion assays of Drp1-101AP antibody. FabGennix Int. Inc., has a wide range of antibodies and reagents for biomedical research community, for a complete listing please visit www.FabGenix.Com.
For research use only, not for diagnostic or therapeutic use.
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