title: The scale-free dynamics of eukaryotic cells.
abstract: Temporal organization of biological processes requires massively parallel processing on a synchronized time-base. We analyzed time-series data obtained from the bioenergetic oscillatory outputs of Saccharomyces cerevisiae and isolated cardiomyocytes utilizing Relative Dispersional (RDA) and Power Spectral (PSA) analyses. These analyses revealed broad frequency distributions and evidence for long-term memory in the observed dynamics. Moreover RDA and PSA showed that the bioenergetic dynamics in both systems show fractal scaling over at least 3 orders of magnitude, and that this scaling obeys an inverse power law. Therefore we conclude that in S. cerevisiae and cardiomyocytes the dynamics are scale-free in vivo. Applying RDA and PSA to data generated from an in silico model of mitochondrial function indicated that in yeast and cardiomyocytes the underlying mechanisms regulating the scale-free behavior are similar. We validated this finding in vivo using single cells, and attenuating the activity of the mitochondrial inner membrane anion channel with 4-chlorodiazepam to show that the oscillation of NAD(P)H and reactive oxygen species (ROS) can be abated in these two evolutionarily distant species. Taken together these data strongly support our hypothesis that the generation of ROS, coupled to redox cycling, driven by cytoplasmic and mitochondrial processes, are at the core of the observed rhythmicity and scale-free dynamics. We argue that the operation of scale-free bioenergetic dynamics plays a fundamental role to integrate cellular function, while providing a framework for robust, yet flexible, responses to the environment.
authors.affiliation: The Johns Hopkins University Institute of Molecular Cardiobiology, Baltimore, MD, USA. maon1@jhmi.edu
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Aon
authors.forename: Marc R
authors.initials: MR
authors.lastname: Roussel
authors.forename: Sonia
authors.initials: S
authors.lastname: Cortassa
authors.forename: Brian
authors.initials: B
authors.lastname: O'Rourke
authors.forename: Douglas B
authors.initials: DB
authors.lastname: Murray
authors.forename: Manfred
authors.initials: M
authors.lastname: Beckmann
authors.forename: David
authors.initials: D
authors.lastname: Lloyd
mesh_terms: D000818:Animals; D001683:Biological Clocks / Q000502:physiology*; D004734:Energy Metabolism; D005057:Eukaryotic Cells / Q000166:cytology / Q000378:metabolism*; D017709:Fractals; D006168:Guinea Pigs; D008564:Membrane Potentials / Q000502:physiology; D008928:Mitochondria / Q000378:metabolism; D008954:Models, Biological; D032383:Myocytes, Cardiac / Q000166:cytology / Q000378:metabolism; D009249:NADP / Q000378:metabolism; D010507:Periodicity; D017382:Reactive Oxygen Species / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000378:metabolism*; D013438:Sulfhydryl Compounds / Q000378:metabolism
chemical_list: D017382:Reactive Oxygen Species; D013438:Sulfhydryl Compounds; D009249:NADP