ABSTRACT

Mitochondria are uniquely poised to play a pivotal role in cell survival or death, because they are regulators of several key cellular processes such as energy metabolism, reduction-oxidation potential, and apoptotic pathways. Maintaining

17.1 Mitochondria .............................................................................................. 391 17.1.1 Mitochondrial Functions-Brief Overview ................................. 391 17.1.2 Mitochondrial ROS Signaling ...................................................... 393

17.2 Mitochondria in AD ................................................................................... 396 17.2.1 Mitochondrial Abnormalities and Oxidative Stress in AD .......... 396 17.2.2 Mitochondrial ROS Signaling and Modulation of Neuronal

Homeostasis .................................................................................. 398 17.2.2.1 Mitochondrial Preconditioning..................................... 399 17.2.2.2 Mitohormesis: Caloric Restriction and Physical

Exercise....................................................................... 402 17.3 Concluding Remarks ..................................................................................403 References ..............................................................................................................404

mitochondrial homeostasis and bioenergetics in neurons is even more critical, because of their almost complete dependence on mitochondrial-derived ATP (Budd and Nicholls 1998; Sullivan et al. 1998; Moreira et al. 2007a). However, the production of energy is accompanied by the generation of reactive oxygen species (ROS) as by-products of the oxidative phosphorylation system (Figure 17.1). ROS are mainly produced at the respiratory chain complexes I and III, where electrons derived from NADH and succinate can directly react with oxygen or other electron acceptors and generate free radicals (Kushnareva et al. 2002; Chen et al. 2003).