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Loss of PLA2G6 leads to elevated mitochondrial lipid peroxidation and mitochondrial dysfunction.

Kinghorn KJ, Castillo-Quan JI, Bartolome F, Angelova PR, Li L, Pope S, Cochemé HM, Khan S, Asghari S, Bhatia KP, Hardy J, Abramov AY, Partridge L - Brain (2015)

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.

View Article: PubMed Central - PubMed

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 k.kinghorn@ucl.ac.uk.

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iPLA2-VIA−/− flies have reduced ATP levels and are more sensitive to oxidative stress. (A) ATP levels are reduced in the heads of Day 25 iPLA2-VIA−/− flies compared with age-matched w1118 control flies (*P < 0.05). (B) Aged Day 15 iPLA2-VIA−/− flies show reduced survival when treated with 5% hydrogen peroxide (H2O2) (P = 5.6 × 10−7) and (C) 20 mM paraquat (P = 4.6 × 10−7) compared with w1118 control flies (n = 150 flies per genotype).
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awv132-F4: iPLA2-VIA−/− flies have reduced ATP levels and are more sensitive to oxidative stress. (A) ATP levels are reduced in the heads of Day 25 iPLA2-VIA−/− flies compared with age-matched w1118 control flies (*P < 0.05). (B) Aged Day 15 iPLA2-VIA−/− flies show reduced survival when treated with 5% hydrogen peroxide (H2O2) (P = 5.6 × 10−7) and (C) 20 mM paraquat (P = 4.6 × 10−7) compared with w1118 control flies (n = 150 flies per genotype).

Mentions: In keeping with the mitochondrial dysfunction caused by loss of iPLA2-VIA activity, we also demonstrated that ATP levels in aged, Day 25, iPLA2-VIA−/− fly heads were reduced by 40% compared with control flies (Fig. 4A). Levels were also reduced in whole iPLA2-VIA−/− flies compared with controls (Supplementary Fig. 3A).Figure 4


Loss of PLA2G6 leads to elevated mitochondrial lipid peroxidation and mitochondrial dysfunction.

Kinghorn KJ, Castillo-Quan JI, Bartolome F, Angelova PR, Li L, Pope S, Cochemé HM, Khan S, Asghari S, Bhatia KP, Hardy J, Abramov AY, Partridge L - Brain (2015)

iPLA2-VIA−/− flies have reduced ATP levels and are more sensitive to oxidative stress. (A) ATP levels are reduced in the heads of Day 25 iPLA2-VIA−/− flies compared with age-matched w1118 control flies (*P < 0.05). (B) Aged Day 15 iPLA2-VIA−/− flies show reduced survival when treated with 5% hydrogen peroxide (H2O2) (P = 5.6 × 10−7) and (C) 20 mM paraquat (P = 4.6 × 10−7) compared with w1118 control flies (n = 150 flies per genotype).
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4559908&req=5

awv132-F4: iPLA2-VIA−/− flies have reduced ATP levels and are more sensitive to oxidative stress. (A) ATP levels are reduced in the heads of Day 25 iPLA2-VIA−/− flies compared with age-matched w1118 control flies (*P < 0.05). (B) Aged Day 15 iPLA2-VIA−/− flies show reduced survival when treated with 5% hydrogen peroxide (H2O2) (P = 5.6 × 10−7) and (C) 20 mM paraquat (P = 4.6 × 10−7) compared with w1118 control flies (n = 150 flies per genotype).
Mentions: In keeping with the mitochondrial dysfunction caused by loss of iPLA2-VIA activity, we also demonstrated that ATP levels in aged, Day 25, iPLA2-VIA−/− fly heads were reduced by 40% compared with control flies (Fig. 4A). Levels were also reduced in whole iPLA2-VIA−/− flies compared with controls (Supplementary Fig. 3A).Figure 4

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.

View Article: PubMed Central - PubMed

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 k.kinghorn@ucl.ac.uk.

Show MeSH
Related in: MedlinePlus