Oxidative stress and mitochondrial dysfunction as determinants of ischemic neuronal death and survival

• Published in: Journal of neurochemistry Vol. 109; no. s1; pp. 133 - 138
• Main Authors: Niizuma, Kuniyasu, Endo, Hidenori, Chan, Pak H
• Format: Journal Article
• Language: English
• Published: Oxford, UK Oxford, UK : Blackwell Publishing Ltd 01.05.2009; Blackwell Publishing Ltd
• Subjects: Animals; apoptosis; Apoptosis Regulatory Proteins; Apoptosis Regulatory Proteins - physiology; bcl-2-Associated X Protein; bcl-2-Associated X Protein - physiology; Biochemistry; Brain damage; Brain Ischemia; Brain Ischemia - metabolism; Brain Ischemia - pathology; Carrier Proteins; Carrier Proteins - physiology; Cell Death; Cell Death - physiology; Cell Survival; Cell Survival - physiology; Death Domain Receptor Signaling Adaptor Proteins; Humans; ischemia; metabolism; mitochondria; Mitochondria - metabolism; Mitochondria - physiology; Neurology; Neurons; Neurons - physiology; Oxidation; oxidative stress; Oxidative Stress - physiology; p53; pathology; physiology; Proto-Oncogene Proteins; Proto-Oncogene Proteins - physiology; reactive oxygen species; Signal Transduction; Signal Transduction - physiology; Superoxide Dismutase; Superoxide Dismutase - metabolism; Superoxide Dismutase-1
• ISSN: 0022-3042; 1471-4159; 1471-4159
• DOI: 10.1111/j.1471-4159.2009.05897.x

Mitochondria are the powerhouse of the cell. Their primary physiological function is to generate adenosine triphosphate through oxidative phosphorylation via the electron transport chain. Reactive oxygen species generated from mitochondria have been implicated in acute brain injuries such as stroke and neurodegeneration. Recent studies have shown that mitochondrially-formed oxidants are mediators of molecular signaling, which is implicated in the mitochondria-dependent apoptotic pathway that involves pro- and antiapoptotic protein binding, the release of cytochrome c, and transcription-independent p53 signaling, leading to neuronal death. Oxidative stress and the redox state of ischemic neurons are also implicated in the signaling pathway that involves phosphatidylinositol 3-kinase/Akt and downstream signaling, which lead to neuronal survival. Genetically modified mice or rats that over-express or are deficient in superoxide dismutase have provided strong evidence in support of the role of mitochondrial dysfunction and oxidative stress as determinants of neuronal death/survival after stroke and neurodegeneration.