Oxidative stress and mitochondrial dysfunction in neurodegeneration; cardiolipin a critical target?
Oxidative stress and subsequent impairment of mitochondrial function is implicated in the neurodegenerative process and hence in diseases such as Parkinson's and Alzheimer's disease. Within the brain, neuronal and astroglial cells can display a differential susceptibility to oxidant exposure. Thus, astrocytes can up regulate glutathione availability and, in response to mitochondrial damage, glycolytic flux. Whilst neuronal cells do not appear to possess such mechanisms, neuronal glutathione status may be enhanced due to the trafficking of glutathione precursors from the astrocyte. However, when antioxidants reserves are not sufficient or the degree of oxidative stress is particularly great, mitochondrial damage occurs, particularly at the level of complex IV (cytochrome oxidase). Whilst the exact mechanism for the loss of activity of this enzyme complex is not know, it is possible that loss and/or oxidative modification of the phospholipid, cardiolipin is a critical factor. Consequently, in this short article, we also consider (a) cardiolipin metabolism and function, (b) the susceptibility of this molecule to undergo oxidative modification following exposure to oxidants such as peroxynitrite, (c) loss of mitochondrial cardiolipin in neurodegenerative disorders, (d) methods of detecting cardiolipin and (e) possible therapeutic strategies that may protect cardiolipin from oxidative degradation.
Pope
Simon
S
Neurometabolic Unit, National Hospital, UCLH Foundation Trust, UCL, Queen Square, London, WC1N 3BG, UK.
Land
John M
JM
Heales
Simon J R
SJ
D000818:Animals; D001253:Astrocytes / Q000502:physiology; D002308:Cardiolipins / Q000502:physiology*; D004734:Energy Metabolism; D006801:Humans; D008928:Mitochondria / Q000502:physiology*; D009410:Nerve Degeneration / Q000503:physiopathology*; D009474:Neurons / Q000502:physiology; D010084:Oxidation-Reduction; D018384:Oxidative Stress
D002308:Cardiolipins