Ketogenesis-generated β-hydroxybutyrate is an epigenetic regulator of CD8 + T-cell memory development | Nature Cell Biology
“Glycogen has long been considered to have a function in energy metabolism. However, our recent study indicated that glycogen metabolism, directed by cytosolic phosphoenolpyruvate carboxykinase Pck1, controls the formation and maintenance of CD8+ memory T (Tmem) cells by regulating redox homeostasis1. This unusual metabolic program raises the question of how Pck1 is upregulated in CD8+ Tmem cells. Here, we show that mitochondrial acetyl coenzyme A is diverted to the ketogenesis pathway, which indirectly regulates Pck1 expression. Mechanistically, ketogenesis-derived β-hydroxybutyrate is present in CD8+ Tmem cells; β-hydroxybutyrate epigenetically modifies Lys 9 of histone H3 (H3K9) of Foxo1 and Ppargc1a (which encodes PGC-1α) with β-hydroxybutyrylation, upregulating the expression of these genes.”