Introduction to Special Issue on Mitochondrial Redox Signaling in Health and Disease
Juan P. Bolañosa, , Enrique Cadenasb, , Michael R. Duchenc, , Mark B. Hamptond, , Giovanni E. Manne, , Michael P. Murphyf,
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http://dx.doi.org/10.1016/j.freeradbiomed.2016.08.004
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Mitochondria are functional entities that harbor the energy-conservation machinery that supports cell function through the coordination of mitochondrion-derived molecules involved in the regulation of cell signaling and transcription. Conversely, mitochondria are targets of an ever-increasing number of signaling pathways and their activity is also modulated by several transcription factors. The cell’s energy-redox homeostasis is primarily a function of mitochondrial oxidative phosphorylation and the formation of O2.–/H2O2. Notably, other mitochondrion-driven processes contribute to cellular homeostasis, such as mitochondrial biogenesis and dynamics, mitochondrial quality control (autophagy and mitophagy), mitochondrial proteostasis and the role of the mitochondrial unfolded protein response (UPRmt), and redox signaling in the homeostatic control of mitochondrial function. This Free Radical Biology & Medicine special issue on Mitochondrial Redox Signaling in Health and Disease covers some aspects of the myriad of processes embraced by mitochondrial biology and physiology, provides mechanistic insights linking mitochondrial function with cell function, and recognizes mitochondrial function as an amenable therapeutic target.
- Energy metabolism: Mitochondria and the organelle network
Mitochondrial function cannot be viewed as that originating from isolated organelles, for extensive cross-regulation of organelle function occurs at organelle contact sites, e.g., MAM (mitochondria-associated membranes) between mitochondria and ER [1]. Other organelle interactions involve the ER, Golgi apparatus, nucleus, plasma membrane and others, and are associated with the regulation of several cellular processes. These organelle contact sites acquire further significance when considering that they serve as a platform for cell signaling, as in the case of MAM alterations and processes associated with insulin resistance [2].
The most important function of mitochondria is oxidative phosphorylation with formation of ATP to maintain the cell’s energy homeostasis: electrons flowing through the respiratory chain complexes linked with pumping of H+ across the inner mitochondrial membrane and energy conservation as a protonmotive force drives the synthesis of ATP. The complexity of the oxidative phosphorylation system has revealed the occurrence of supercomplexes with different proportions of complexes I, III, and IV [3] and [4], the formation of which is assisted by several assembly factors. The occurrence of two different coenzyme Q pools (one trapped within the supercomplex structure and another free in the inner mitochondrial membrane) serves to reconcile diverging experimental evidences under the plasticity model [5]. It may be surmised that supercomplex organization is an adaptive mechanism of mitochondria to optimize their function in response to fuel availability and/or oxidant concentration [5]. Mitochondrial translation is essential for the oxidative phosphorylation system biogenesis and, consequently, for cellular energy supply. The synthesis of mtDNA-encoded polypeptide subunits of oxidative phosphorylation complexes is supported by a key quality control factor in mitochondrial translation, the mitochondrial translation factor 4 (mtEF4) [6], which –together with other translational activators– facilitates the crosstalk between mitochondrial translation and cytosolic translation, a process regulated by mTOR signaling [6].
full article http://www.sciencedirect.com/science/article/pii/S089158491630377X