UC San Diego

Cardiomyocytes are under constant mechanical and metabolic stress, which makes functional protein quality control (PQC) systems particularly important. Molecular chaperones and co-chaperones are essential components of a functioning PQC. Mutation and downregulation of the co-chaperone protein BCL-2–associated athanogene 3 (BAG3) are associated with cardiomyopathy and heart failure. It has been reported that a BAG3 P209L missense mutation leads to the development of myofibrillar myopathy with severe cardiac defects. However, the mechanisms by which the P209L mutation leads to cardiomyopathy remain obscure. In our present study, we found that BAG3 P209L mutation in mice did not cause cardiomyopathy. In the molecular level, the levels of ATP-dependent and ATP-independent heat shock proteins were not changed in cardiac tissues from BAG3 P209L mutant mice. Further experiments revealed that the P209L mutation did not influence the levels of autophagy or global ubiquitination in cardiac tissues. Together, these observations suggest that the BAG3 209L mutation alone may not cause cardiomyopathy in mice.