PUBLICATION
Myoglobin modulates the Hippo pathway to promote cardiomyocyte differentiation
- Authors
- Rao, K., Rochon, E., Singh, A., Jagannathan, R., Peng, Z., Mansoor, H., Wang, B., Moulik, M., Zhang, M., Saraf, A., Corti, P., Shiva, S.
- ID
- ZDB-PUB-240228-13
- Date
- 2024
- Source
- iScience 27: 109146109146 (Journal)
- Registered Authors
- Keywords
- Biochemistry, Biological sciences, Cell biology, Natural sciences, Specialized functions of cells
- MeSH Terms
- none
- PubMed
- 38414852 Full text @ iScience
Citation
Rao, K., Rochon, E., Singh, A., Jagannathan, R., Peng, Z., Mansoor, H., Wang, B., Moulik, M., Zhang, M., Saraf, A., Corti, P., Shiva, S. (2024) Myoglobin modulates the Hippo pathway to promote cardiomyocyte differentiation. iScience. 27:109146109146.
Abstract
The endogenous mechanisms that propagate cardiomyocyte differentiation and prevent de-differentiation remain unclear. While the expression of the heme protein myoglobin increases by over 50% during cardiomyocyte differentiation, a role for myoglobin in regulating cardiomyocyte differentiation has not been tested. Here, we show that deletion of myoglobin in cardiomyocyte models decreases the gene expression of differentiation markers and stimulates cellular proliferation, consistent with cardiomyocyte de-differentiation. Mechanistically, the heme prosthetic group of myoglobin catalyzes the oxidation of the Hippo pathway kinase LATS1, resulting in phosphorylation and inactivation of yes-associated protein (YAP). In vivo, myoglobin-deficient zebrafish hearts show YAP dephosphorylation and accelerated cardiac regeneration after apical injury. Similarly, myoglobin knockdown in neonatal murine hearts shows increased YAP dephosphorylation and cardiomyocyte cycling. These data demonstrate a novel role for myoglobin as an endogenous driver of cardiomyocyte differentiation and highlight myoglobin as a potential target to enhance cardiac development and improve cardiac repair and regeneration.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping