Non-metabolic role of a glycolysis enzyme, pyruvate

Pyruvate is a final  metabolite of glycolysis involved in cellular energetics but its non-metabolic functions remain unexplored.

In this study, the researchers demonstrate  a post-translational modification (PTM) function of pyruvate in protein pyruvylation.

They show pyruvylation of signal transducer and activator of transcription 1 (STAT1) at Lys201 (K201) at high glucose concentration. This pyruvylation blocks STAT1 and signal transducer and activator of transcription 2 (STAT2) interaction, thus suppressing type I interferon (IFN-I) signaling and antiviral immune activity.

The authors also demonstrate that STAT1-K201R knockin mice exhibit enhanced IFN-I antiviral immunity.

This study thus identifies the protein pyruvylation modification, reveals a non-metabolic function of the metabolite pyruvate in an anti-viral immunity.

 https://www.cell.com/cell/fulltext/S0092-8674(26)00110-8

https://sciencemission.com/Pyruvate-is-a-natural-suppressor-of-interferon-signaling