Phospho-DRP1 (Ser637) Antibody

Dynamin-related protein 1 (DRP1) is a member of the dynamin superfamily of GTPases. Members of this family have diverse cellular functions including vesicle scission, organelle fission, viral resistance, and intracellular trafficking (reviewed in 1). DRP1 affects mitochondrial morphology and is important in mitochondrial and peroxisomal fission in mammalian cells (2-5). The yeast ortholog of DRP1 clusters into a spiral-shaped structure on the mitochondrial membrane at the site of fission (reviewed in 6), and this structure is likely conserved in mammalian cells (3). The division of the mitochondria, which is required for apoptosis, as well as normal cell growth and development is controlled, in part, by the phosphorylation of DRP1 at Ser616 by Cdk1/cyclin B and at Ser637 by protein kinase A (PKA) (reviewed in 6). When phosphorylated at Ser616, DRP1 stimulates mitochondrial fission during mitosis. Conversely, fission is inhibited when DRP1 is phosphorylated at Ser637 (reviewed in 6). Dephosphorylation at Ser637 by calcineurin reverses this inhibition (7). In addition to phosphorylation, sumoylation of DRP1 is also an enhancer of mitochondrial fission (8). Balancing fission and fusion events is essential for proper mitochondrial function. Research studies have demonstrated mitochondrial defects in a variety of neurodegenerative diseases including Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease (reviewed in 6). 1.Praefcke, G.J. and McMahon, H.T. (2004) Nat Rev Mol Cell Biol 5, 133-47. 2.Taguchi, N. et al. (2007) J Biol Chem 282, 11521-9. 3.Smirnova, E. et al. (2001) Mol Biol Cell 12, 2245-56. 4.Smirnova, E. et al. (1998) J Cell Biol 143, 351-8. 5.Koch, A. et al. (2003) J Biol Chem 278, 8597-605. 6.Knott, A.B. et al. (2008) Nat Rev Neurosci 9, 505-18. 7.Cereghetti, G.M. et al. (2008) Proc Natl Acad Sci USA 105, 15803-8. 8.Zunino, R. et al. (2007) J Cell Sci 120, 1178-88.