Fig. 3: CHCHD2 deletion or PD-linked T61I mutation result in KGDH deficiency in human dopaminergic neurons and mouse brains. | Nature Communications

Fig. 3: CHCHD2 deletion or PD-linked T61I mutation result in KGDH deficiency in human dopaminergic neurons and mouse brains.

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

Fig. 3

A–E Immunoblots and quantifications of OGDHL, OGDH, DLST and DLD protein levels in control and CHCHD2-deficient human dopaminergic (DA) neurons. N = 4 biological replicates. Data shown are mean ± SEM. Two-sided t test. F, G KGDH enzyme activities in control and CHCHD2-deficient dopaminergic neurons. N = 6 biological replicates. Data shown are mean ± SEM. Two-sided t test. H–L Immunoblots and quantifications of Chchd2, Ogdh, Dlst and Dld protein levels in striatum of wildtype (WT) and Chchd2 T61I/+ knock-in (KI) mice. n = 3 mice. Data shown are mean ± SEM. Two-sided t test. M–R Immunoblots and quantifications of CHCHD2, OGDHL, OGDH, DLST, and DLD protein levels in DA neurons derived from patient iPSC line with PD-linked CHCHD2 T61I/+ mutation (T61I/ + PD) and mutation-corrected isogenic controls (iso ctrl). N = 3 biological replicates for 3 N and 3 P, and 6 biological replicates for 3 O, 3Q, and 3 R. Data shown are mean ± SEM. Two-sided t test. S–X The levels of unlabeled (M + 0) and 13C labeled (M + N) pyruvate, citrate/iso citrate, α-KG, succinate, fumarate and malate in T61I/ + PD and isogenic control DA neurons after 6 h of labeling with U-13C6 glucose. The levels of metabolites were normalized by the levels of 13C6 glucose for each sample. N = 4 biological replicates. All 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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