Study reveals phosphofructokinase condensation is regulated by metabolic and redox signals in yeast
Researchers have found that phosphofructokinase, the rate-limiting enzyme of glycolysis, forms granules in yeast cells in response to metabolic state and reactive oxygen species signaling, not only under stress conditions as previously thought. The study shows granule formation is linked to the cell's metabolic strategy — particularly during the transition from fermentation to respiration — and requires the disordered N-terminus of one subunit (Pfk1) for assembly. These findings challenge existing assumptions about when and why this key metabolic enzyme condenses, with implications for understanding how cells regulate energy metabolism.
A new preprint study from bioRxiv investigated the mechanisms governing condensation of phosphofructokinase (PFK), the rate-limiting enzyme of glycolysis, into granules in yeast. Contrary to the prevailing view that PFK granule formation is restricted to quiescent or stressed cells, the researchers found that the two PFK subunits — Pfk1 and Pfk2 — can assemble into granules even without exogenous stress, and that this process is independent of cell division. Granules were found to be most prevalent in replicatively aged cells but could form both before and after cells stop dividing. The study also demonstrated that granule formation is strongly suppressed in cells undergoing respiration or lacking respiratory capacity, yet is sharply induced during the metabolic shift from fermentation to respiration, suggesting tight coupling between condensation and metabolic strategy. Additionally, reactive oxygen species (ROS) signaling via superoxide dismutase 1 (Sod1) was found to modulate granule assembly, as Sod1-deficient cells showed impaired condensation. Structurally, Pfk2 was shown to depend on the disordered N-terminus of Pfk1 for co-assembly into the same granules. Taken together, the findings reframe PFK condensation as a dynamic, regulated process rather than a passive stress response.
What's missing
As a preprint, this study has not yet undergone peer review, and its findings should be interpreted with caution. The study is conducted entirely in yeast (Saccharomyces cerevisiae), and it remains unclear whether similar regulatory mechanisms govern PFK condensation in mammalian or other eukaryotic cells. The functional consequences of granule formation — whether it activates, inhibits, or sequesters PFK activity — are not fully resolved. The precise molecular mechanism by which Sod1-mediated ROS signaling influences granule assembly is also not established.
What different sources said
- bioRxivCenter
Dynamics of phosphofructokinase condensation are regulated by metabolic and redox cues
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