Energetics of the failing heart: new insights using genetic modification in the mouse

Genetic modification in the mouse heart has provided new and important insights into many aspects of ATP synthesis, supply and utilization and how this changes in the failing heart. Here, three topics based on recent literature will be reviewed: direct manipulation of precursor pool for creatine; the path linking creatine, purine nucleotides and metabolic remodeling; and long-term reprogramming of ATP synthesis pathways. These examples illustrate the value of deleting, over-expressing and mutating specific proteins in our quest for understanding the energetics of the failing heart.