Poster 19
Presenter: Nikki Walter
Wednesday, 3:00 – 5:00pm
K.J. Buck; N.A.R. Walter; D.L. Denmark Department of Behavioral Neuroscience and Portland Alcohol Research Center, Portland VA Medical Center and Oregon Health & Science University, Portland, OR 97239
Arrangement into stable and specific multicomplex assemblies is a fundamental property of the mitochondrial respiratory chain (RC) with significant functional implications. Genetic RC defects and associated reactive oxygen species (ROS) production underlie the debilitating consequences of the most prevalent group of inborn errors of metabolism and are central pathogenic themes in a multitude of progressive conditions, e.g., aging, cancer, and neurodegeneration. While many causal genes are now known, elucidation of their etiological mechanisms is just beginning. We assessed brain RC complexes with blue native electrophoresis (BNE) and in-gel activity (IGA) staining in two highly relevant genetic mouse models known to diverge in ROS-related traits, the C57BL6/J (B6) and DBA/2J (D2) inbred strains. These studies reveal marked qualitative and semi-quantitative differences in complex III and IV interactions affecting multiple assemblies, including respirasomes, and suggest overall organization is relatively less fixed in B6 than D2. To our knowledge, these are the first comparative analyses of RC suprastructure in mammalian brain, particularly in a genotype-dependent context. Furthermore, these data suggest brain RC may exist within a range of genetically influenced plasticity that is relevant both to adaptive energetic and oxidative homeostasis in mice, and potentially mitochondrial-related disease in humans.