The Calcineurin-FoxO-MuRF1 signaling pathway regulates myofibril integrity in cardiomyocytes.

ABSTRACT: Altered Ca²⁺ handling is often present in diseased hearts undergoing structural remodeling and functional deterioration. However, whether Ca²⁺ directly regulates sarcomere structure has remained elusive. Using a zebrafish ncx1 mutant, we explored the impacts of impaired Ca²⁺ homeostasis on myofibril integrity. We found that the E3 ubiquitin ligase murf1 is upregulated in ncx1-deficient hearts. Intriguingly, knocking down murf1 activity or inhibiting proteasome activity preserved myofibril integrity, revealing a MuRF1-mediated proteasome degradation mechanism that is activated in response to abnormal Ca²⁺ homeostasis. Furthermore, we detected an accumulation of the murf1 regulator FoxO in the nuclei of ncx1

SUBMITTER: Shimizu H 

PROVIDER: S-EPMC5576919 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature