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: Light microscopic examination of thin paraffin sections of iPLA2-VIA−/− fly brain revealed normal brain architecture in young Day 2 flies that was indistinguishable from w1118 controls (Fig. 2A and B). However, by Day 32 there was significant widespread vacuolation in the iPLA2-VIA−/− fly brains that was not present in w1118 control flies (Fig. 2C and D). Ultrastructural examination using electron microscopy revealed that the mitochondria were grossly abnormal and swollen with fragmented cristae in aged Day 32 iPLA2-VIA−/− fly brains as compared to the mitochondria in age-matched w1118 control brains (Fig. 2E–H) or younger Day 2 iPLA2-VIA−/− flies (data not shown), which were both filled with densely packed cristae. Furthermore, examination of the fly eye using electron microscopy revealed abnormal retinal structure in the aged Day 32 iPLA2-VIA−/− flies compared with age-matched control flies, with grossly abnormal ommatidial structure (Supplementary Fig. 2A and B).Figure 2
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.