The scale-free dynamics of eukaryotic cells

dc.contributor.authorAon, Miguel A.
dc.contributor.authorRoussel, Marc R.
dc.contributor.authorCortassa, Sonia
dc.contributor.authorO'Rourke, Brian
dc.contributor.authorMurray, Douglas B.
dc.contributor.authorBeckmann, Manfred
dc.contributor.authorLloyd, David
dc.descriptionSherpa Romeo green journal: open accessen_US
dc.description.abstractTemporal 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.en_US
dc.identifier.citationAon, M. A., Roussel, M. R., Cortassa, S., O'Rourke, B., Murray, D. B., Beckmann, M., & Lloyd, D. (2008). The scale-free dynamics of eukaryotic cells. PLoS ONE, 3(11), e3624. doi:10.1371/journal.pone.0003624en_US
dc.publisherPublic Library of Scienceen_US
dc.publisher.departmentDepartment of Chemistry and Biochemistryen_US
dc.publisher.facultyArts and Scienceen_US
dc.publisher.institutionJohns Hopkins University Institute of Molecular Cardiobiologyen_US
dc.publisher.institutionUniversity of Lethbridgeen_US
dc.publisher.institutionKeio Universityen_US
dc.publisher.institutionUniversity of Walesen_US
dc.publisher.institutionCardiff Universityen_US
dc.subjectScale-free dynamicsen_US
dc.subjectEukaryotic cellsen_US
dc.subjectFractal scalingen_US
dc.subjectHeart cellsen_US
dc.subjectRelative dispersional analysisen_US
dc.subjectPower spectral analysisen_US
dc.titleThe scale-free dynamics of eukaryotic cellsen_US
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