EMBO Molecular Medicine· 2026Q1
Lysine pyruvylation: decoding the molecular language of pyruvate signaling
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- 2026year
Short summary
Lysine pyruvylation (Kpy) is a newly identified protein modification that links cellular metabolism to regulatory circuits, with initial evidence showing it can suppress immune signaling and affect gene transcription.
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Key points
- Lysine pyruvylation (Kpy) converts pyruvate availability into a reversible protein modification.
- Kpy of STAT1 suppresses type I interferon signaling by disrupting STAT1–STAT2 assembly.
- Histone Kpy, mediated by HAT1 and SIRT3, links glycolytic flux to active chromatin and transcription.
- Kpy is proposed as an interface between metabolism, chromatin, and immunity.
AI-generated from the title and abstract; the full text is not read.
Abstract
Lysine pyruvylation (Kpy) converts pyruvate availability into a reversible protein modification, placing a central carbon metabolite directly within cellular regulatory circuits. An initial study identified STAT1 K201 pyruvylation and showed that this modification suppresses type I interferon signaling by disrupting STAT1–STAT2 assembly. A subsequent study established HAT1 and p300 as Kpy writers and SIRT3 as a Kpy eraser, linking histone Kpy to glycolytic flux, active chromatin and transcription. Together, these findings introduce Kpy as a potential interface between metabolism, chromatin and immunity. However, evidence is currently limited to two initial mechanistic studies: disease causality, abundance and occupancy in human tissues, and translational utility remain unestablished. This commentary therefore distinguishes demonstrated mechanisms from testable hypotheses and outlines the evidence required before Kpy can be considered a disease biomarker or therapeutic target. In this Comment article, Jun Zhang discusses the emerging role of lysine pyruvylation as a metabolic regulator and outlines the key evidence needed to establish its relevance as a biomarker and therapeutic target in human disease.
The authors' abstract, as published at the source. EMBO Molecular Medicine, 2026 · DOI ↗
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Field: Biochemistry (Biochemistry, Genetics and Molecular Biology)
BiochemistryBiochemistry, Genetics and Molecular Biology