The fundamental organization of cardiac mitochondria as a network of coupled oscillators

¹ Johns Hopkins University

^* To whom correspondence should be addressed. E-mail: bor{at}jhmi.edu.

Submitted on April 24, 2006
Revised on May 16, 2006
Accepted on 29 August 2006

	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 (_m) in cardiomyocytes under physiological conditions is oscillatory, characterized by a broad frequency distribution that obeys a homogeneous power law (1/ f ) with a spectral exponent, = 1.74. Additionally, relative dispersional analysis shows that mitochondrial oscillatory dynamics exhibit 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 (ROS) production and scavenging. The results demonstrate that cardiac mitochondria behave as a network of coupled oscillators under both physiological and pathophysiological conditions.

Key Words: inverse power law, mitochondrial oscillator, pink, brown and white noises., power spectral analysis, reactive oxygen species, relative dispersional analysis