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. 2019 May 1;39(18):3561–3581. doi: 10.1523/JNEUROSCI.1983-18.2019

Figure 4.

Figure 4.

Expression of components of the SLC25A1-SLC25A4 interactome is affected in neurodevelopmental disorders. A, Comprehensive in silico interactome of the SLC25A1 and SLC25A4 mitochondrial transporters. Complexes I to V of the respiratory chain as well as SLC25A transporter family members are color coded. All nodes colored gray represents hits in the 22q11.2 proteome. Additional details can be found in Figure 4-1. B, Expression of SLC25A transporter family member transcripts is altered in SLC25A1 or SLC25A4-null cells. Transcript quantification by qRT-PCR is expressed as a ratio to vimentin mRNA. VAMP3 was used as control. n = 4; one-way ANOVA followed by Fisher's least significant difference comparison. All nonsignificant comparisons are marked (NS). C, Expression of SLC25A transporter family member polypeptides is altered in Df(16)A+/− mouse hippocampus (Hipp) or prefrontal cortex (PFC). SLC25A transporters were quantitated by TMT mass spectrometry. n = 6 mutant and 5 control mice; one-way ANOVA followed by Fisher's least significant difference comparison. *p ≤ 0.0001, **p = 0.0098, ***p ≤ 0.028. D, Expression of SLC25A family member mRNAs is reduced in whole blood from unaffected and 22q11.2 patients. Probability plots of mRNA quantified by microarray on 50 unaffected (gray) and 77 22q11.2 patients (blue). SNAP29, MRPL40, and SLC25A1 reside in the 22q11.2 microdeletion locus and were used as controls to determine the range of expression change attributable to the microdeletion. SLC25A3 and SLC25A25 expression is modified within this range. P values were calculated using Kolmogorov–Smirnov test. E, mRNA expression of SLC25A transporters in gray matter or single cells isolated from unaffected and schizophrenia cases. Gray matter mRNA quantitations were performed by RNAseq, whereas single-cell mRNA quantitations were performed by microarray in dorsolateral prefrontal cortex (DLPFC) samples. F, Proteomic quantitation of SLC25A transporters in iPSC-derived cortical neurons from DISC-1 mutant patient and isogenic controls. E, F, SLC25A transporter family members SLC25An where n correspond to the number on blue circle. Gray box denotes nonsignificant changes in expression after multiple corrections. G, mRNA expression of SLC25A transporter family members is altered in schizophrenia brains. Meta-analysis data obtained from Gandal et al. (2018).