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
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.
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mbCRISPR22-mbmbCRISPR
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Name Type Antigen Genes Isotypes Host Organism
Ab1-mef2polyclonal
    IgGRabbit
    Ab1-N2.261monoclonal
      IgG1Mouse
      Ab2-pcnamonoclonalIgG2aMouse
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