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About the Authors:
Jiyeong Kim
Contributed equally to this work with: Jiyeong Kim, Su-Kyung Kim
Affiliation: Department of Life Science, College of Natural Sciences, Ewha Womans University, Seoul, South Korea
Su-Kyung Kim
Contributed equally to this work with: Jiyeong Kim, Su-Kyung Kim
Affiliation: Department of Life Science, College of Natural Sciences, Ewha Womans University, Seoul, South Korea
Hwa-Kyung Kim
Affiliation: Department of Life Science, College of Natural Sciences, Ewha Womans University, Seoul, South Korea
Mark P. Mattson
Affiliation: Laboratory of Neurosciences, National Institute on Aging Intramural Research Program, National Institutes of Health, Baltimore, Maryland, United States of America
Dong-Hoon Hyun
* E-mail: [email protected]
Affiliation: Department of Life Science, College of Natural Sciences, Ewha Womans University, Seoul, South Korea
Introduction
Mitochondria are a hub for cellular energy metabolism because they produce the majority of ATP required for cell survival and maintenance of cell physiology [1], [2]. However, during oxidative phosphorylation, mitochondria generate free radicals, which can cause oxidative damage and mitochondrial dysfunction. Alterations in mitochondrial function and energy metabolism are believed to contribute to aging and age-related diseases [3], [4]. Defective activities of mitochondrial complexes I, II, III and IV have been identified in several major neurodegenerative diseases and to a lesser extent during normal aging [5], [6], [7], [8], and may result in reductions of ATP levels and ATP-dependent biochemical processes [9]. In addition, neurons are very vulnerable to acute oxidative and metabolic stresses that may occur under conditions of ischemia or hypoglycemia [1], [10]. It is therefore important to understand mechanisms by which neurons can maintain mitochondrial function under stressful conditions.
In contrast to postmitotic neurons, tumor cells are relatively resistant to metabolic and oxidative stress, in part because their mitochondria-mediated programmed cell death pathways are often disabled [11], [12]. Cellular energy metabolism is also typically altered in cancer cells such that glycolysis is increased and oxidative phosphorylation reduced [12].
The PMRS (plasma membrane redox system) can regulate redox homeostasis by promoting maintenance of a relatively high NAD+/NADH ratio [13]. In response to oxidative stress, electrons are transferred across the plasma membrane, from internal reductants such as NAD(P)H to external oxidants [14], [15], [16]. Coenzyme Q (CoQ), a key electron shuttle in the plasma membrane, can be reduced either by NAD(P)H-quinone oxidoreductase 1 (NQO1)...