The homeodomain transcription factor Pitx2 regulates left-right asymmetry during heart morphogenesis and its loss leads to severe cardiovascular defects. In addition to this developmental role, it was recently shown to have a protective function during heart regeneration following injury; however, the long-term consequences of Pitx2 depletion on cardiac repair were not clear. Now, James F. Martin and colleagues address this issue by inducing infarcts in neonatal mice and looking at cardiac repair 60 days post injury. They find that hearts in which the cardiomyocytes have Pitx2 conditionally knocked out accumulate adipose-like cells of non-cardiomyocyte origin in the scar tissue – implying a non-cell autonomous role for Pitx2 in this context. Further, Pitx2 knockout also compromises mitochondrial function. Importantly, the authors link the adipose-like phenotype to impaired mitochondrial function by showing that mice heterozygous for the Pitx2 target Cox7c, a mitochondrial gene, also accumulate fat during cardiac regeneration. Thus, this work not only adds to our understanding of Pitx2 functions in the heart, but also reveals the importance of mitochondrial function during heart repair, with implications for diseases that are affected by intramyocardial and epicardial fat tissue accumulation (e.g. atrial fibrillation).