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. 2019 Oct 4;116(10):1742–1755. doi: 10.1093/cvr/cvz251

Figure 7.

Figure 7

Oxidation at Cys1483 of mTOR mediates inhibition of metabolic gene promoter activity in the absence of Trx1. (A) Cys1483 forms an intermolecular disulphide in response to Trx1 knockdown. Myc-mTOR-C1483F was expressed in H9c2 cells via plasmid vector transfection, and then Trx1 was knocked down with shTrx1 adenovirus. Ratio of oxidized/reduced form of mTOR is indicated (N = 5). (B–C) Trx1 knockdown-induced mTOR inhibition is normalized by mTOR-C1483F. Myc-mTOR-C1483F and GST-HA-S6K were expressed in H9c2 cells (B) and cardiomyocytes (C) via plasmid vector transfection, and then Trx1 was knocked down with shTrx1 adenovirus. Phosphorylation of GST-HA-S6K was examined. (B, Right) Densitometric analysis of phosphorylated S6K in H9c2 cells (N = 8–9). (D) Trx1 knockdown-induced inhibition of Ndfua1 and Ndufs1 reporter gene activity is normalized by mTOR-C1483F (N = 6). (E) Schematic representation of Trx1-mediated metabolic gene expression. Trx1 prevents oxidation at Cys1483 in mTOR, thereby maintaining mTOR-induced metabolic gene expression. Statistical significance was determined with one-way ANOVA followed by Tukey test (A, B, and D). *P<0.05 and ***P<0.001.