Mitochondrial Protein Acetylation and Sirtuin-Mediated Deacetylation

Heart and lung physiological function provides through blood hemoglobin the convective transport of O2 to tissues. Within cells, O2 diffuses to mitochondria where it is reduced to H2O coupled with adenosine triphosphate (ATP) synthesis in the energy-yielding process of oxidative phosphorylation. Mitochondria are by far the largest cell consumers of O2 and the determinants of cytosolic PO2 and of the O2 gradient between alveoli and cells. Mitochondria control cell survival by providing the ATP required for endergonic processes and the molecular signals that command genetic expression and metabolic regulation (Darley-Usmar 2004). Superoxide radical (O2-) is generated through the monovalent reduction of O2 in the mitochondrial electron transport chain, mainly by auto oxidation of the semiquinones of ubiquinone (UQH·) and of avin mononucleotide (FMNH·), in a process by which rate is determined by the metabolic state and the redox state of the mentioned respiratory chain components (Boveris, Oshino, and Chance 1972). The enhanced mitochondrial 9.1 Introduction .................................................................................................. 169 9.2 Nitric Oxide Production and Effectors in the Heart ..................................... 172 9.2.1 Nitric Oxide Synthases ..................................................................... 172 9.2.2 Downstream Signaling Pathways of NO .......................................... 173 9.3 Heart Mitochondrial NO Production ............................................................ 174 9.4 Heart NO Metabolism in Hypoxic States ..................................................... 175 9.4.1 Cardioprotection with PDE5 Inhibitors ............................................ 180 9.5 Concluding Remarks .................................................................................... 183 Acknowledgments .................................................................................................. 183 References .............................................................................................................. 184 generation of O2-and hydrogen peroxide (H2O2), the product of O2-dismutation, appears implicated in the onset of both deleterious and cardioprotective mechanisms within the heart (Bell, Emerling, and Chandel 2005). H2O2 and nitric oxide (NO) are uncharged molecules normally produced in mitochondria that are highly diffusible through biological membranes and suitable for subcellular and cellular signaling.