PGM1 deficiency is linked to sarcomeric and mitochondrial dysfunction in patient-derived iPSC-cardiomyocytes - PubMed
9 hours ago
- #Cardiomyopathy
- #Mitochondrial dysfunction
- #PGM1-CDG
- PGM1 deficiency is associated with cardiomyopathy and persists despite galactose therapy correcting glycosylation defects.
- PGM1-deficient iPSC-derived cardiomyocytes (iCMs) show reduced beating frequency, impaired contractility, and prolonged contraction kinetics.
- Proteomic analyses reveal depletion of Z-disk components, including LDB3, and mitochondrial proteins in PGM1-deficient iCMs.
- AlphaFold3 modeling predicts a direct interaction between PGM1 and LDB3, linking PGM1 to Z-disk integrity.
- Mitochondrial function is severely impaired in PGM1-deficient iCMs, with metabolic rewiring and energy depletion.
- In silico drug repurposing identifies potential therapeutic options for PGM1-deficient cardiomyopathy.
- PGM1 is a key regulator of cardiomyocyte function, connecting sarcomeric Z-disk integrity with mitochondrial metabolism.