Figure 3.

SOX17 (SRY-related HMG-box 17) augments oxidative phosphorylation and mitochondrial function in endothelial cells. (A) Gene Ontology analysis highlights metabolic processes as the top targets of SOX17 deficiency. (B) PAECs were transduced with increasing multiplicities of infection (MOIs) of AdSOX17. Western blot analysis was used to confirm the overexpression of SOX17. An MOI of 20 was used. (C) A heatmap illustrating alterations in metabolite concentrations in SOX17-overexpressed endothelial cells (ECs) compared with control ECs. (D) Targeted gas chromatography–mass spectrometry analysis identifies increases in TCA cycle metabolites in SOX17 overexpressing ECs. (E–I) Increasing SOX17 expression enhances mitochondrial bioenergetics (E), as determined by increases in basal oxygen consumption rate (OCR) (F), OCR for ATP generation (G), and reserve (H) and MAX (I) respiratory capacity. Data are represented as mean ± SEM. ****P < 0.0001. 3PG = 3-phosphoglyceric acid; AdSOX17 = adenovirus containing human SOX17; CoA = coenzyme A; MAX = maximal; PAEC = pulmonary artery endothelial cell; PEP = phosphoenolpyruvate; TCA = tricarboxylic acid.