As hypoxia exposure increases, sirtuin 4 (SIRT4) gene expression also increases, and Hogan et al. (198) showed that the administration of MSC-secreted exosomes to PASMCs inhibited SIRT4 and pyruvate dehydrogenase kinase 4 (PDK4) expression, upregulated pyruvate dehydrogenase (PDH) and glutamate dehydrogenase 1 (GLUD1) expression levels, allowed glutamine and pyruvate to enter the TCA cycle and improved mitochondrial dysfunction associated with PAH. The gene discussed is SIRT4; the disease is pulmonary arterial hypertension.