Oxidative phosphorylation is required for cardiomyocyte re-differentiation and long-term fish heart regeneration.

ABSTRACT: In contrast to humans, fish can fully regenerate their hearts after cardiac injury. However, not all fish have the same regenerative potential, allowing comparative inter-species and intra-species analysis to identify the mechanisms controlling successful heart regeneration. Here we report a differential regenerative response to cardiac cryo-injury among different wild-type zebrafish strains. Correlating these data with single-cell and bulk RNA sequencing data, we identify oxidative phosphorylation (OXPHOS) as a positive regulator of long-term regenerative outcome. OXPHOS levels, driven by glycolysis through the malate-aspartate shuttle, increase as soon as cardiomyocyte proliferation decreases, and this increase is required for cardiomyocyte re-differentiation and successful long-term reg

SUBMITTER: Lekkos K 

PROVIDER: S-EPMC12520976 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature