Aging process modulates nonlinear dynamics in liver cell metabolism.
Regulatory dynamics of energy metabolism in living cells entails a coordinated response of multiple enzyme networks that operate under non-equilibrium conditions. Here we show that mitochondrial dysfunctions associated with the aging process significantly modify nonlinear dynamical signatures in free radical generation/removal, thereby altering energy metabolism in liver cells. We support our data with a plausible biochemical mechanism for modified bioenergetics that involves uncoupling protein-2 that is up-regulated in aged cells as an adaptive response to mitigate increased oxidative stress. Combining high spatial and temporal resolution imaging and bio-energetic measurements, our work provides experimental support to the hypothesis that mitochondria manifest nonlinear dynamical behavior for efficiently regulating energy metabolism in intact cells, and any partial or complete reduction in this behavior would contribute to organ dysfunctions including the aging process and other disease processes.
Ramanujan
V Krishnan
VK
Department of Cellular and Structural Biology, University of Texas Health Science Center, San Antonio, Texas 78229, USA.
Herman
Brian A
BA
D000818:Animals; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000502:physiology*; D004734:Energy Metabolism / Q000502:physiology*; D006019:Glycolysis / Q000502:physiology; D022781:Hepatocytes / Q000166:cytology* / Q000378:metabolism*; D007473:Ion Channels / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000378:metabolism; D008954:Models, Biological; D017711:Nonlinear Dynamics; D010084:Oxidation-Reduction; D010085:Oxidative Phosphorylation; D018384:Oxidative Stress / Q000502:physiology; D000071246:Uncoupling Protein 2; D015854:Up-Regulation / Q000502:physiology
D007473:Ion Channels; D024101:Mitochondrial Proteins; C000604390:Ucp2 protein, mouse; D000071246:Uncoupling Protein 2