Although individual deletion of either Ppargc1a or Ppargc1b genes in rodent models does not lead to significant cardiac alterations due to the functional redundancy [5,6,7], their relevance in the control of cardiac energetics is demonstrated in mice simultaneously devoid of both PGC-1 co-activators specifically in cardiac cells, which die early after birth from heart failure [3]. The gene discussed is PPARGC1A; the disease is heart failure.