Abstract
In this chapter, we introduce a network view of mitochondrial function that includes consideration of how the spatial and temporal organization of mitochondria is crucial for understanding the behavior of living cells. The network is characterized by applying advanced experimental techniques - including optical mapping, patch-clamp techniques, and two-photon microscopy - combined with mathematical methods, including computational modeling, power spectral analysis, and relative dispersion analysis for studying complex nonlinear interactions with the potential for self-organized behavior. Remarkably, the mitochondrial network is shown to have scale-free fractal characteristics in both time and space that govern the timing and extent of functional synchronization between individual organelles. This new framework is applied not only to better understand the established role of mitochondria in bioenergetics but also to reveal a novel physiological signaling system centered on reactive oxygen species (ROS) and how this system can undergo a transition to a critical pathophysiological state under metabolic stress. The major insight from these studies is that mitochondria act as a network of coupled oscillators with the potential for active intracellular ROS signaling through a frequency- and amplitude-encoded process. These newly identified spatiotemporal features of mitochondria extend the traditional view as mere ATP generators to explain their impact on signaling, cell injury, cell death, and whole-organ dysfunction associated with aging and a variety of diseases.
Original language | English (US) |
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Title of host publication | Molecular System Bioenergetics |
Subtitle of host publication | Energy for Life |
Publisher | Wiley-VCH Verlag GmbH & Co. KGaA |
Pages | 111-135 |
Number of pages | 25 |
ISBN (Print) | 9783527317875 |
DOIs | |
State | Published - Nov 22 2007 |
Keywords
- Biological oxidation
- Cellular energetics
- Dynamics
- Inner membrane ion channels
- Intracellular signaling
- Mitochondrial morphodynamics
- Mitochondrial network dynamics
- Molecular system bioenergetics
- Network properties mitochondria
- Organization
- Outer membrane ion channels
ASJC Scopus subject areas
- General Biochemistry, Genetics and Molecular Biology