Fig. 4: Membrane lipids containing Long-Chain Polyunsaturated Fatty Acids, including phosphoinositides species are decreased in pathogenic Auxilin fly heads. | npj Parkinson's Disease

Fig. 4: Membrane lipids containing Long-Chain Polyunsaturated Fatty Acids, including phosphoinositides species are decreased in pathogenic Auxilin fly heads.

From: Parkinsonism mutations in DNAJC6 cause lipid defects and neurodegeneration that are rescued by Synj1

Fig. 4

a Pie diagram of the relative abundance of individual GL and GPL classes in 15DO wild-type fly heads detected by mass spectrometry (MS). n = 7 analyses and one individual analysis is performed on 15 fly heads collected from 3 independent crosses. b. The relative abundance of individual GL and GPL classes in 15DO fly heads of indicated genotypes relative to dAuxWT/WT and dAuxWT/F as detected by mass spectrometry (MS). Bars show mean ± SEM of n ≥ 4 analyses. One individual analysis is performed on 15 fly heads collected from 3 independent crosses. Two-way ANOVA, Tukey’s multiple comparison test. **p < 0.01. c Schematic of the geometry of membrane lipids, showing the effect of polar headgroups and fatty acyl side chains. Membrane thickness, fluidity and deformity is influenced by the saturation level and length of the fatty acyl chain in concert with the presence of cholesterol55. d, e Saturation level (d) and length (e) of fatty acyl chains of all membrane lipids are presented as fraction of total membrane GL + GPL. Bars show mean ± SEM. n ≥ 4 and one individual analysis is performed on 15 fly heads. MUFA, mono-unsaturated; PUFA, poly-unsaturated. Two-way ANOVA, Tukey’s multiple comparison test. *p < 0.05. f, g Length (f) and saturation level (g) of fatty acyl chains of PI ad PE are presented as fraction of total membrane GL + GPL. Note the lower levels of LC-PUFAs including PI LC-PUFAs in dAux mutants. Plus, neuronal Synj expression partially rescues pathogenic dAuxRG/F956x mutant. Bars show mean ± SEM. n ≥ 4 analyses for dAuxWT/WT, dAuxRG/RG, dAuxWT/F956x and dAuxRG/F956x and n = 3 for dAuxWT/F956x and dAuxRG/F956x overexpressing Synj in neurons. One individual analysis is performed on 15 fly heads collected from 3 independent crosses. Two-way ANOVA, Tukey’s multiple comparison test. ns: not significant, *p < 0.05, **p < 0.01, ***p < 0.001 and ****p < 0.0001. # indicates comparison with dAuxRG/F956x. ns: not significant, #p < 0.05, ##p < 0.01 and ###p < 0.001.

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