Fig. 4: Deficiency of CHCHD2 but not CHCHD10 leads to elevated lipid peroxidation. | Nature Communications

Fig. 4: Deficiency of CHCHD2 but not CHCHD10 leads to elevated lipid peroxidation.

From: Dysregulation of mitochondrial α-ketoglutarate dehydrogenase leads to elevated lipid peroxidation in CHCHD2-linked Parkinson’s disease models

Fig. 4

A Alterations of metabolites of CHCHD2-deficient cells are highlighted by red arrows. Created in BioRender. Gao, G. (2025) https://BioRender.com/t66n226. B Histograms of the intensities of oxidized and reduced C11-BODIPY signals of control and CHCHD2-deficient HEK293T cells under DMSO- and RSL3-induced conditions. The ratio of oxidized to reduced C11-BODIPY fluorescence intensities of control and two CHCHD2 knockout clones of HEK293T cells under DMSO- (C) and RSL3-treated (D) conditions. N = 12, 10 and 6 biological replicates for control, D2 KO #1 and D2 KO #2, respectively. All data shown are mean ± SEM. One-way ANOVA with Dunnett’s test. E, F The ratio of oxidized to reduced C11-BODIPY fluorescence intensities of control and CHCHD2 KO #1 HEK293T cells under RSL3- or ML162-stressed conditions treated with or without iron chelator deferoxamine (DFO). N = 5 and 4 biological replicates for (E, F), respectively. All data shown are mean ± SEM. One-way ANOVA with Dunnett’s test. G Representative images of oxidized and reduced C11-BODIPY signals of control and CHCHD2-deficient human dopaminergic neurons under DMSO- and RSL3-treated conditions. Scale bar, 20 μm. N = 3 independent experiments. H The ratio of oxidized to reduced C11-BODIPY fluorescence intensities of control and CHCHD2-deficient dopaminergic neurons under basal (left) and RSL3-treated (right) conditions. Images were collected and analyzed from N = 3 independent experiments. Data shown are mean ± SEM. Two-sided t test. I Representative images of oxidized and reduced C11-BODIPY signals of DA neurons with CHCHD2 T61I mutation and isogenic controls under basal condition. Scale bar, 20 μm. N = 3 independent experiments. J The ratio of oxidized to reduced C11-BODIPY fluorescence intensities of T61I/ + PD and isogenic control DA neurons. Images were collected and analyzed from N = 3 independent experiments. Data shown are mean ± SEM. Two-sided t test. K Histograms of the intensities of oxidized and reduced C11-BODIPY signals of control and CHCHD10-deficent HEK293T cells under basal and RSL3-induced conditions. The ratio of oxidized to reduced C11-BODIPY fluorescence intensities of control and CHCHD10-deficient cells under basal (L) and RSL3-treated (M) conditions. N = 3 independent experiments. Data shown are mean ± SEM. ns, not significant. Two-sided t test. Source data are provided as a Source Data file.

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