Extended Data Fig. 4: Peroxidase activity of cyt c–MLCL complex causes phospholipid peroxidation in vitro and induces changes in lipidome and oxy-lipidome of genetically manipulated yeast.
From: Anomalous peroxidase activity of cytochrome c is the primary pathogenic target in Barth syndrome
MS/MS spectra of (a) HOO-MLCL(L)3 (left panel) and oxidatively truncated ONA-MLCL(L)3 (right panel), (b) PC(18:0/18:2-OOH) (left panel) and PE(18:0/18:2-OOH) (right panel), (c) PC(18:0/ONA) (left panel) and PE(18:0/ONA) (right panel). Possible structures of oxidation products are inserted. ONA- 9-oxo nonanoic acid. d, Typical MS spectra of CL (upper panels) and MLCL (lower panels) obtained from yeast cells. e, Effect of D12desaturase on composition of CL (left panel) and MLCL (right panel) in WT and taz1D yeasts. SFA – saturated fatty acids, MUFA – monounsaturated fatty acids, PUFA – polyunsaturated fatty acids. f, Content of PC (upper panels) and PE (lower panels) molecular species in WT and D12/taz1D cells. Data are presented as mean values ± SD. Each data point represents a biologically independent sample. Upper panels: left ****P < 0.0001, middle ****P < 0.0001, ***P = 0.0004, right *P = 0.0202, ***P = 0.0001. ****P < 0.0001. One-way ANOVA, Tukey’s multiple comparison test. Lower panels; left ****P < 0.0001, middle **P = 0.0115. ***P = 0.0006, unpaired two-tailed t-test, ***P < 0.0001, ****P < 0.0001, One-way ANOVA, Tukey’s multiple comparison test. right ***P = 0.0056, unpaired two-tailed t-test, ****P < 0.0001, One-way ANOVA, Tukey’s multiple comparison test. g, OPLS-DA analysis showing the differences in oxy-lipidomes of D12 and D12/taz1D yeast cells; h, Pie plots showing the number of oxidatively modified phospholipid species. In total, 60 oxygenated phospholipid species were detected in yeast cells.
