A metabolite-pair controlled quiescence switch via ATP-dependent phase separation

Prof. Zengyi Chang published a paper in Scientific Reports.

Amino acid oxidation during carbon starvation inevitably generates NH₄⁺ and HCO₃⁻ as byproducts. Here we show that this metabolite pair acts synergistically to deplete cellular ATP, a task neither accomplishes alone. Rather than nutrient starvation itself, it is this specific energy crisis that triggers quiescence. ATP depletion relieves the nucleotide’s previously described function as a biological hydrotrope—independent of its hydrolysis—that normally maintains the solubility of a defined subset of proteins. The resulting selective phase separation assembles regrowth-delay (RD) bodies, which sequester key growth-related proteins and enforce a reversible dormant state. Crucially, restoration of ATP levels fully dissolves these condensates and permits resumption of growth, with initial ATP levels in dormant cells predicting awakening times. Strikingly, this NH₄⁺/HCO₃⁻-dependent pathway also induces a reversible quiescent state in yeast, suggesting a conserved metabolite-controlled dormancy switch across biological kingdoms.