PKM1 is required for embryonic cardiomyocyte proliferation through energetic regulation of NFYa stability.

ABSTRACT: Pyruvate kinase M1 (PKM1) is a critical enzyme in glycolysis, particularly in high-energy-demand tissues like the heart. However, previous knockout strategies for PKM1 were confounded by compensatory upregulation of its low-activity splice variant, PKM2. Here, we generated a Pkm1 mutant mouse model using a point mutation that eliminates PKM1 without compensatory PKM2 upregulation. Homozygous Pkm1 mutants exhibited perinatal lethality associated with cardiac dysfunction, characterized by thin myocardium and reduced cardiomyocyte proliferation during mid-to-late gestation. We found that PKM1 sustains ATP levels to inhibit AMPK, which otherwise promotes NFYa phosphorylation and destabilization. NFYa, a transcription factor essential for cardiomyocyte proliferation, has been iden

SUBMITTER: Zhang D 

PROVIDER: S-EPMC12796809 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature