The return of quiescence metabolites

Abstract

The transition of endothelial cells between quiescence and proliferation is essential for regulating the extent of the vasculature that supplies oxygen and nutrients to tissues. A study now shows that the FOXO1 transcription factor regulates endothelial cell proliferation by controlling levels of the metabolite 2-hydroxyglutarate.

Figure 1.

Schematic of proposed regulatory pathway. In Andrade et al., the authors propose a regulatory pathway in the endothelial cells that line blood vessels. The FOXO1 transcription factor increases the expression of metabolic enzymes that generated catabolic intermediates of branched chain amino acids such as 3-methyl-2-oxovalerate (KMV). Elevated levels of these intermediates inhibit the activity of the oxoglutarate dehydrogenase (OGDH) complex. Reduced activity of this complex results in an accumulation of S-2-hydroxyglutarate (S-2HG), which can promote endothelial cell quiescence.