title: The fundamental organization of cardiac mitochondria as a network of coupled oscillators.
abstract: Mitochondria can behave as individual oscillators whose dynamics may obey collective, network properties. We have shown that cardiomyocytes exhibit high-amplitude, self-sustained, and synchronous oscillations of bioenergetic parameters when the mitochondrial network is stressed to a critical state. Computational studies suggested that additional low-amplitude, high-frequency oscillations were also possible. Herein, employing power spectral analysis, we show that the temporal behavior of mitochondrial membrane potential (DeltaPsi(m)) in cardiomyocytes under physiological conditions is oscillatory and characterized by a broad frequency distribution that obeys a homogeneous power law (1/f(beta)) with a spectral exponent, beta = 1.74. Additionally, relative dispersional analysis shows that mitochondrial oscillatory dynamics exhibits long-term memory, characterized by an inverse power law that scales with a fractal dimension (D(f)) of 1.008, distinct from random behavior (D(f) = 1.5), over at least three orders of magnitude. Analysis of a computational model of the mitochondrial oscillator suggests that the mechanistic origin of the power law behavior is based on the inverse dependence of amplitude versus frequency of oscillation related to the balance between reactive oxygen species production and scavenging. The results demonstrate that cardiac mitochondria behave as a network of coupled oscillators under both physiological and pathophysiological conditions.
authors.affiliation: Johns Hopkins University Institute of Molecular Cardiobiology, Baltimore, MD 21205-2195, USA.
authors.forename: Miguel Antonio
authors.initials: MA
authors.lastname: Aon
authors.forename: Sonia
authors.initials: S
authors.lastname: Cortassa
authors.forename: Brian
authors.initials: B
authors.lastname: O'Rourke
mesh_terms: D000818:Animals; D001703:Biophysics / Q000379:methods*; D005456:Fluorescent Dyes / Q000737:chemistry; D006168:Guinea Pigs; D053078:Membrane Potential, Mitochondrial; D018613:Microscopy, Confocal; D008928:Mitochondria / Q000378:metabolism*; D008954:Models, Biological; D008955:Models, Cardiovascular; D032383:Myocytes, Cardiac / Q000378:metabolism*; D009991:Oscillometry; D017785:Photons; D017382:Reactive Oxygen Species; D012984:Software; D013997:Time Factors
chemical_list: D005456:Fluorescent Dyes; D017382:Reactive Oxygen Species