Targeting S-Nitrosylated PKM2: A Novel Therapeutic Frontier in Cardiac Fibrosis and Mitochondrial Dynamics

MedXY Editorial Team•Mar 3, 2026•Cardiology

S-nitrosylation (SNO) of Pyruvate Kinase Isoform 2 (PKM2) at Cys49 and Cys326 is a specific hallmark of activated cardiac fibroblasts in heart failure.
SNO-PKM2 disrupts PKM2 tetramerization and reduces enzyme activity, shifting the metabolic and structural state of the cell.
Mechanistically, SNO-PKM2 promotes excessive mitochondrial fission by interfering with the actin regulatory protein gelsolin, leading to mitochondrial dysfunction and fibroblast activation.
The FDA-approved drug mitapivat and the activator TEPP-46 effectively reverse these pathways, presenting a viable therapeutic strategy for mitigating cardiac fibrosis.

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MedXY Editorial Team•Mar 3, 2026•Cardiology

S-nitrosylation (SNO) of Pyruvate Kinase Isoform 2 (PKM2) at Cys49 and Cys326 is a specific hallmark of activated cardiac fibroblasts in heart failure.
SNO-PKM2 disrupts PKM2 tetramerization and reduces enzyme activity, shifting the metabolic and structural state of the cell.
Mechanistically, SNO-PKM2 promotes excessive mitochondrial fission by interfering with the actin regulatory protein gelsolin, leading to mitochondrial dysfunction and fibroblast activation.
The FDA-approved drug mitapivat and the activator TEPP-46 effectively reverse these pathways, presenting a viable therapeutic strategy for mitigating cardiac fibrosis.

MedXY registered readers

Create or use your MedXY account to unlock the complete article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

Open language-specific specialty feeds and department pages.

Loading comments...