Department of Microbiology and Molecular Medicine, Faculty of Medicine, University of Geneva, Geneva, Switzerland
Julian Pezzatti
Institute of Pharmaceutical Sciences of Western Switzerland (ISPSO), University of Geneva, Geneva, Switzerland
Víctor González-Ruiz
Institute of Pharmaceutical Sciences of Western Switzerland (ISPSO), University of Geneva, Geneva, Switzerland; Swiss Centre for Applied Human Toxicology (SCAHT), Basel, Switzerland
Laurence Degeorges
Department of Microbiology and Molecular Medicine, Faculty of Medicine, University of Geneva, Geneva, Switzerland
Geneviève Mottet-Osman
Department of Microbiology and Molecular Medicine, Faculty of Medicine, University of Geneva, Geneva, Switzerland
Serge Rudaz
Institute of Pharmaceutical Sciences of Western Switzerland (ISPSO), University of Geneva, Geneva, Switzerland; Swiss Centre for Applied Human Toxicology (SCAHT), Basel, Switzerland
Proliferating cells must coordinate central metabolism with the cell cycle. How central energy metabolism regulates bacterial cell cycle functions is not well understood. Our forward genetic selection unearthed the Krebs cycle enzyme citrate synthase (CitA) as a checkpoint regulator controlling the G1→S transition in the polarized alpha-proteobacterium Caulobacter crescentus, a model for cell cycle regulation and asymmetric cell division. We find that loss of CitA promotes the accumulation of active CtrA, an essential cell cycle transcriptional regulator that maintains cells in G1-phase, provided that the (p)ppGpp alarmone is present. The enzymatic activity of CitA is dispensable for CtrA control, and functional citrate synthase paralogs cannot replace CitA in promoting S-phase entry. Our evidence suggests that CitA was appropriated specifically to function as a moonlighting enzyme to link central energy metabolism with S-phase entry. Control of the G1-phase by a central metabolic enzyme may be a common mechanism of cellular regulation.
