| Autor: |
Jason W. Miklas, Shiri Levy, Peter Hofsteen, Diego Ic Mex, Elisa Clark, Jeanot Muster, Aaron M. Robitaille, Gargi Sivaram, Lauren Abell, Jamie M. Goodson, Inez Pranoto, Anup Madan, Michael T. Chin, Rong Tian, Charles E. Murry, Randall T. Moon, Yuliang Wang, Hannele Ruohola-Baker |
| Jazyk: |
angličtina |
| Rok vydání: |
2022 |
| Předmět: |
|
| Zdroj: |
iScience, Vol 25, Iss 1, Pp 103574- (2022) |
| Druh dokumentu: |
article |
| ISSN: |
2589-0042 |
| DOI: |
10.1016/j.isci.2021.103574 |
| Popis: |
Summary: Heart disease is the leading cause of death with no method to repair damaged myocardium due to the limited proliferative capacity of adult cardiomyocytes. Curiously, mouse neonates and zebrafish can regenerate their hearts via cardiomyocyte de-differentiation and proliferation. However, a molecular mechanism of why these cardiomyocytes can re-enter cell cycle is poorly understood. Here, we identify a unique metabolic state that primes adult zebrafish and neonatal mouse ventricular cardiomyocytes to proliferate. Zebrafish and neonatal mouse hearts display elevated glutamine levels, predisposing them to amino-acid-driven activation of TOR, and that TOR activation is required for zebrafish cardiomyocyte regeneration in vivo. Through a multi-omics approach with cellular validation we identify metabolic and mitochondrial changes during the first week of regeneration. These data suggest that regeneration of zebrafish myocardium is driven by metabolic remodeling and reveals a unique metabolic regulator, TOR-primed state, in which zebrafish and mammalian cardiomyocytes are regeneration competent. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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