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: A mutant fly stock completely lacking the Drosophila orthologue of the PLA2G6 gene, iPLA2-VIA, was obtained from the Bloomington Drosophila Stock Centre. We will refer to mutant flies lacking both iPLA2-VIA genes as iPLA2-VIA−/− henceforth. This fly strain carries a P-element insertion (EY05103) in the iPLA2-VIA gene (Fig. 1A). As previously shown, RT-PCR analysis confirmed that there was complete knockout of iPLA2-VIA gene expression in this strain with no detectable SYBR green signal produced. The end products of the RT-PCR reactions were also visualized on agarose gel electrophoresis, which confirmed the complete absence of iPLA2-VIA gene expression in the iPLA2-VIA−/− flies (Fig. 1B) (Malhotra et al., 2009). Knockout of iPLA2-VIA activity in the fly did not produce any gross changes in body size or obvious differences in morphology (data not shown). iPLA2-VIA is expressed throughout the adult fly body, including the brain and eye. The iPLA2-VIA gene displays good homology with the human PLA2G6 gene, with a 51% identity and 67% positivity (FlyBase).Figure 1
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.