Loss of PLA2G6 leads to elevated mitochondrial lipid peroxidation and mitochondrial dysfunction.
Bottom Line: Furthermore, we demonstrate that loss of iPLA2-VIA function leads to a number of mitochondrial abnormalities, including mitochondrial respiratory chain dysfunction, reduced ATP synthesis and abnormal mitochondrial morphology.Moreover, we show that loss of iPLA2-VIA is strongly associated with increased lipid peroxidation levels.Similar abnormalities were seen including elevated mitochondrial lipid peroxidation and mitochondrial membrane defects, as well as raised levels of cytoplasmic and mitochondrial reactive oxygen species.
Affiliation: 1 Institute of Healthy Ageing and Department of Genetics, Evolution and Environment, University College London, London WC1E 6BT, UK 2 Institute of Neurology, University College London, Queen Square, London WC1N 3BG, UK firstname.lastname@example.org.Show MeSH
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Mentions: Following the demonstration that there is an increase in lipid peroxidation in the brains of flies lacking iPLA2-VIA compared with controls, we also assessed lipid peroxidation in two human PLA2G6 fibroblast lines; one taken from a patient with dystonia-parkinsonism with a p.R747W mutation (Paisan-Ruiz et al., 2009) and the other from a child with infantile neuroaxonal dystrophy. We assessed lipid peroxidation levels using the fluorescent ratiometric oxidation-sensitive C11 BODIPY581/591 dye. This demonstrated that PLA2G6 mutant fibroblasts had an increased level of lipid peroxidation compared to controls (Fig. 7A), suggesting therefore that lipid peroxides may be a potential therapeutic target.Figure 7
Affiliation: 1 Institute of Healthy Ageing and Department of Genetics, Evolution and Environment, University College London, London WC1E 6BT, UK 2 Institute of Neurology, University College London, Queen Square, London WC1N 3BG, UK email@example.com.