Fig. 4: PCCB knockdown leads to mitochondrial dysfunction and decreased GABA levels in U2F hFOs. | Nature Communications

Fig. 4: PCCB knockdown leads to mitochondrial dysfunction and decreased GABA levels in U2F hFOs.

From: Human forebrain organoid-based multi-omics analyses of PCCB as a schizophrenia associated gene linked to GABAergic pathways

Fig. 4

a RT-qPCR analysis revealed downregulated expression of mitochondrial genes in PCCB knockdown hFOs. b, c Decreased ATP (b) and increased ROS contents (c) were observed in PCCB knockdown hFOs. d, e, f ELISA analysis validated the reduction of α-KG (d), SOCA (e), and succinic acid (f) in PCCB knockdown hFOs. g Adding α-KG (10 μg/mL) into the culture medium of PCCB knockdown hFOs restored the GABA levels. h Potential pathways involved in the regulation of PCCB knockdown on GABA synthesis. GAD, glutamate decarboxylase; GABA-T, GABA transaminase; SSA, Succinic semialdehyde; SSADH, succinic semialdehyde dehydrogenase; ↓, downregulation; ↑, upregulation. N ≥ three biologically independent samples in each group. Data are shown as Mean ± SEM. The unpaired two-tailed t-test was used to assess difference between the PCCB-NC and PCCB-G1 or PCCB-G2 group. *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001, ##P < 0.01, ###P < 0.001, $$P < 0.01, $$$P < 0.001. Source data underlying a-g are provided as a Source Data file.

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