Mitochondrial oscillations in physiology and pathophysiology.

Oscillations in chemical reactions and metabolic pathways have historically served as prototypes for understanding the dynamics of complex nonlinear systems. This chapter reviews the oscillatory behavior of mitochondria, with a focus on the mitochondrial oscillator dependent on reactive oxygen species (ROS), as first described in heart cells. Experimental and theoretical evidence now indicates that mitochondrial energetic variables oscillate autonomously as part of a network of coupled oscillators under both physiological and pathological conditions. The physiological domain is characterized by small-amplitude oscillations in mitochondrial membrane potential (delta psi(m)) showing correlated behavior over a wide range of frequencies, as determined using Power Spectral Analysis and Relative Dispersion Analysis of long term recordings of delta psi(m). Under metabolic stress, when the balance between ROS generation and ROS scavenging is perturbed, the mitochondrial network throughout the cell locks to one main low-frequency, high-amplitude oscillatory mode. This behavior has major pathological implications because the energy dissipation and cellular redox changes that occur during delta psi(m) depolarization result in suppression of electrical excitability and Ca2+ handling, the two main functions of the cardiac cell. In an ischemia/reperfusion scenario these alterations scale up to the level of the whole organ, giving rise to fatal arrhythmias.