title: Dynamin-related protein 1 heterozygote knockout mice do not have synaptic and mitochondrial deficiencies.
abstract: The objective of this study was to elucidate the effect of partial reduction of the mitochondrial fission protein, dynamin-related protein 1 (Drp1) on mitochondrial activity and synaptic viability. Recent knockout studies of Drp1 revealed that homozygote Drp1 knockout mice are embryonic lethal due to reduced mitochondrial fission, and that this reduced fission leads to developmental defects in the brain. In contrast, heterozygote Drp1 knockout mice appear to be normal in terms of lifespan, fertility, and viability, and phenotypically these animals are not different from wild-type mice. However, the effects of partial Drp1 reduction on mitochondrial function and synaptic activity are not well understood. In the present study, we sought to characterize synaptic, dendritic and mitochondrial proteins, and mitochondrial function and GTPase enzymatic activity, in Drp1 heterozygote knockout mice. Interestingly, we found no significant changes in synaptic, dendritic, and mitochondrial proteins in the Drp1 heterozygote knockout mice compared to the wild-type mice. Further, mitochondrial function and GTPase enzymatic activity appeared to be normal. However, H(2)O(2) and lipid peroxidation levels were significantly reduced in the Drp1 heterozygote knockout mice compared to the wild-type mice. These findings suggest that partial Drp1 reduction does not affect mitochondrial and synaptic viability and may have therapeutic use in treating patients with Alzheimer's disease and Huntington's disease.
authors.affiliation: Neurogenetics Laboratory, Neuroscience Division, Oregon National Primate Research Center, Oregon Health & Science University, 505 NW 185th Avenue, Beaverton, OR 97006, USA.
authors.forename: Maria
authors.initials: M
authors.lastname: Manczak
authors.forename: Hiromi
authors.initials: H
authors.lastname: Sesaki
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Kageyama
authors.forename: P Hemachandra
authors.initials: PH
authors.lastname: Reddy
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism; D002478:Cells, Cultured; D034281:Dynamins / Q000235:genetics* / Q000378:metabolism*; D003576:Electron Transport Complex IV / Q000378:metabolism; D020558:GTP Phosphohydrolases / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000378:metabolism; D008054:Lipid Peroxides / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress; D013569:Synapses / Q000235:genetics / Q000378:metabolism*
chemical_list: D008054:Lipid Peroxides; D024101:Mitochondrial Proteins; D006861:Hydrogen Peroxide; D003576:Electron Transport Complex IV; D020558:GTP Phosphohydrolases; C486391:Dnm1l protein, mouse; D034281:Dynamins