Light shed on a non-canonical TCA cycle:cell state regulation beyond mitochondrial energy production

A recent publication in Natureby Arnold et al.reports on the discovery of a non-canonical tricarboxylic acid(TCA)cycle in which acetyl-CoA produced from mitochondrially derived citrate by ACLY regenerates_oxaloacetate in the cytoplasm.1 Oxaloacetate is converted through a two-direction reaction to malate,which is uptaken by the mitochondrial citrate/malate transporter SLC25A1 in the mitochondria,where it fuels oxaloacetate and citrate production(Fig.1a).