title: Cell cycle progression is regulated by intertwined redox oscillators.
abstract: The different phases of the eukaryotic cell cycle are exceptionally well-preserved phenomena. DNA decompaction, RNA and protein synthesis (in late G1 phase) followed by DNA replication (in S phase) and lipid synthesis (in G2 phase) occur after resting cells (in G0) are committed to proliferate. The G1 phase of the cell cycle is characterized by an increase in the glycolytic metabolism, sustained by high NAD+/NADH ratio. A transient cytosolic acidification occurs, probably due to lactic acid synthesis or ATP hydrolysis, followed by cytosolic alkalinization. A hyperpolarized transmembrane potential is also observed, as result of sodium/potassium pump (NaK-ATPase) activity. During progression of the cell cycle, the Pentose Phosphate Pathway (PPP) is activated by increased NADP+/NADPH ratio, converting glucose 6-phosphate to nucleotide precursors. Then, nucleic acid synthesis and DNA replication occur in S phase. Along with S phase, unpublished results show a cytosolic acidification, probably the result of glutaminolysis occurring during this phase. In G2 phase there is a decrease in NADPH concentration (used for membrane lipid synthesis) and a cytoplasmic alkalinization occurs. Mitochondria hyperfusion matches the cytosolic acidification at late G1/S transition and then triggers ATP synthesis by oxidative phosphorylation. We hypothesize here that the cytosolic pH may coordinate mitochondrial activity and thus the different redox cycles, which in turn control the cell metabolism.
authors.affiliation: Ecole Polytechnique, LIX-UMR 7161, Palaiseau, France. daveiga@lix.polytechnique.fr.
authors.forename: Jorgelindo
authors.initials: J
authors.lastname: da Veiga Moreira
authors.affiliation: LRI, Paris-Sud University, CNRS UMR8623 and INRIA Saclay, Paris, France. speres@lri.fr.
authors.forename: Sabine
authors.initials: S
authors.lastname: Peres
authors.affiliation: Ecole Polytechnique, LIX-UMR 7161, Palaiseau, France. jean-marc.steyaert@polytechnique.edu.
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Steyaert
authors.affiliation: Ecole Polytechnique, LIX-UMR 7161, Palaiseau, France. bigan.erwan@orange.fr.
authors.forename: Erwan
authors.initials: E
authors.lastname: Bigan
authors.affiliation: Ecole Polytechnique, LIX-UMR 7161, Palaiseau, France. loic.pauleve@lri.fr.|LRI, Paris-Sud University, CNRS UMR8623 and INRIA Saclay, Paris, France. loic.pauleve@lri.fr.
authors.forename: Loïc
authors.initials: L
authors.lastname: Paulevé
authors.affiliation: Ecole Polytechnique, LIX-UMR 7161, Palaiseau, France. marcel.levy@psl.aphp.fr.|Paris Institute of Translationnal Neurosciences (IHU-A-ICM), Pitié Salpêtrière Hospital, Paris, France. marcel.levy@psl.aphp.fr.
authors.forename: Marcel Levy
authors.initials: ML
authors.lastname: Nogueira
authors.affiliation: Ecole Polytechnique, LIX-UMR 7161, Palaiseau, France. laurent.schwartz@polytechnique.edu.
authors.forename: Laurent
authors.initials: L
authors.lastname: Schwartz
mesh_terms: D000244:Adenosine Diphosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D002244:Carbon / Q000378:metabolism; D002453:Cell Cycle; D006863:Hydrogen-Ion Concentration; D042541:Intracellular Space / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism; D010084:Oxidation-Reduction
chemical_list: D000244:Adenosine Diphosphate; D002244:Carbon; D000255:Adenosine Triphosphate