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The Fundamental Organization of Cardiac Mitochondria as a Network of Coupled Oscillators

The Johns Hopkins University Institute of Molecular Cardiobiology, Baltimore, Maryland 21205-2195

Correspondence: Address reprint requests to Brian O'Rourke, PhD, The Johns Hopkins University, 720 Rutland Ave., 1059 Ross Bldg., Baltimore, MD 21205. Tel.: 410-614-0034; Fax: 410-955-7953; E-mail: bor{at}jhmi.edu.

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 (_m) in cardiomyocytes under physiological conditions is oscillatory and characterized by a broad frequency distribution that obeys a homogeneous power law (1/f^ß) with a spectral exponent, ß = 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.