title: Inhibition of mitochondrial respiration by nitric oxide: its role in glucose metabolism and neuroprotection.
abstract: There is an increasing body of evidence demonstrating that inhibition of cytochrome c oxidase by nitric oxide (NO) may be one more step in a signaling cascade involved in the physiologic regulation of cell functions. For example, in both astrocytes and neurons the inhibition of mitochondrial respiration by endogenously produced NO induces transient and modest decreases in cellular ATP concentrations. This mitochondrial impairment may serve as a cellular sensor of energy charges, hence modulating metabolic pathways, such as glycolysis, through AMP-activated protein kinase (AMPK) in astrocytes. In neurons, the NO derivative peroxynitrite anion triggers signaling pathways leading to glucose oxidation through the pentose-phosphate pathway to form reducing equivalents in the form of NADPH. The modulation of these metabolic pathways by nitric oxide or its derivatives may be important for understanding the mechanisms by which this free radical affects neuronal death or survival.
authors.affiliation: Departamento de Bioquímica y Biología Molecular, Universidad de Salamanca, Campus Miguel de Unamuno. 37007 Salamanca, Spain.
authors.forename: Angeles
authors.initials: A
authors.lastname: Almeida
authors.forename: Pilar
authors.initials: P
authors.lastname: Cidad
authors.forename: María
authors.initials: M
authors.lastname: Delgado-Esteban
authors.forename: Emilio
authors.initials: E
authors.lastname: Fernández
authors.forename: Paula
authors.initials: P
authors.lastname: García-Nogales
authors.forename: Juan P
authors.initials: JP
authors.lastname: Bolaños
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D001921:Brain / Q000166:cytology; D005947:Glucose / Q000378:metabolism*; D006706:Homeostasis / Q000502:physiology; D006801:Humans; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D008954:Models, Biological; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009569:Nitric Oxide / Q000096:biosynthesis / Q000502:physiology*; D030421:Peroxynitrous Acid / Q000494:pharmacology / Q000502:physiology; D012119:Respiration / Q000187:drug effects*
chemical_list: D018696:Neuroprotective Agents; D030421:Peroxynitrous Acid; D009569:Nitric Oxide; D005947:Glucose