Life-stage and organ specific changes in mitochondrial bioenergetics in Brown Norway Rats
Citation:
Pandya, J., A. Sebastian, J. Royland, R. MacPhail, P. Sullivan, AND P. Kodavanti. Life-stage and organ specific changes in mitochondrial bioenergetics in Brown Norway Rats. Presented at FASEB Conference on Mitochondrial Biogenesis, Big Sky, MT, June 16 - 21, 2013.
Impact/Purpose:
This abstract will be presented at the FASEB Summer Conference on Mitochondrial Biogenesis in Big Sky Montanna, June 16-21-2013
Description:
Mitochondria are central regulators of energy homeostasis and play a pivotal role in mechanisms of cellular senescence and age-related neurodegenerative and metabolic disorders. However, mitochondrial bioenergetic parameters have not been systematically evaluated under identical physiological conditions within multiple organ samples in diverse age-groups. In the present study, we used the Seahorse Extracellular Flux Analyzer (Seahorse Bioscience XF-24) to compare four different life- stages of Brown Norway rats [i.e. 1 Month- Young (Y), 4 Month- Adult (A), 12 Month- Middle-Aged (M) and 24 Month- Old-Aged (0)]. We measured mitochondrial bioenergetic parameters in five brain regions [brain stem (BS), frontal cortex (FC), cerebellum (CER), striatum (STR), hippocampus (HIP)] and three peripheral organs [heart (HRT), liver (LVR), lung (LNG)]. Ficoll purified mitochondrial samples (15-40 pg/well) from the eight tissues (n=5 animals/group) were analyzed for NADH-Iinked, pyruvate-malate (PM) substrate-driven maximal (State V) respiratory rates, ATP synthesis capacity (State III) and proton leak (State IV). Additionally, FADH-linked maximal respiratory (State Vs) rates were assessed in all samples. In general, all the regions of the brain followed identical patterns where the maximal respiratory capacities (State V and State Vs) were reduced as a function of increasing age (Y>A>M=O). The State III respiration in BS, CER and HIP demonstrated a similar pattern as observed for the maximal respiratory capacities (Y>A>M=O); whereas the FC and STR displayed highest State III rates in adult group amongst all the age groups compared here (A>Y?O?M). The proton leak (State IV) remained unaffected. When respiratory rates were measured in peripheral organs, the State V and State Ill rates were highest in younger animals followed by gradual decline with aging as evident in both HRT (Y>A=O>M) and LNG (Y>A=O=M). In LVR, the FADH-Iinked respiration was predominantly operative than NADH-linked bioenergetics. In LVR, the NADH-Iinked respiratory parameters remained unchanged amongst all the age groups tested; whereas the FADH-Iinked maximal respiratory (State Vs) rates increased gradually as a function of age (Y