Is there a mitochondrial clock?

A mitochondrial oscillator dependent on reactive oxygen species (ROS) was first described in heart cells. Available evidence now indicates that mitochondrial energetic variables oscillate autonomously as part of a network of coupled oscillators under both physiological and pathological conditions. Moreover, emerging experimental and theoretical evidence indicates that mitochondrial network oscillations exhibit a wide range of frequencies, from milliseconds to hours, instead of a dominant frequency. With metabolic stress, the frequency spectrum narrows and a dominant oscillatory frequency appears, indicating the transition from physiological to pathophysiological behavior. Here we show that in the pathophysiological regime the mitochondrial oscillator of heart cells is temperature compensated within the range of 25-37°C with a Q₁₀ = 1.13. At temperatures higher than 37°C, the oscillations stop after a few cycles, whereas at temperatures lower than 25°C the oscillations are asynchronous. Using our mitochondrial oscillator model we show that this temperature compensation can be explained by kinetic compensation. Furthermore, we show that in the physiological domain temperature compensation acts to preserve the broad range of frequencies exhibited by the network of coupled mitochondrial oscillators. The results obtained indicate that the mitochondrial network behaves with the characteristics of a biological clock, giving rise to the intriguing hypothesis that it may function as an intracellular timekeeper across multiple time scales.