Adenylate kinase 1 gene deletion disrupts muscle energetic economy despite metabolic rearrangement

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Abstract
Efficient cellular energy homeostasis is a critical determinant of muscle performance, providing evolutionary advantages responsible for species survival. Phosphotransfer reactions, which couple ATP production and utilization, are thought to play a central role in this process. Here, we provide evidence that genetic disruption of AK1‐catalyzed β‐phosphoryl transfer in mice decreases the potential of myofibers to sustain nucleotide ratios despite up‐regulation of high‐energy phosphoryl flux through glycolytic, guanylate and creatine kinase phosphotransfer pathways. A maintained contractile performance of AK1‐deficient muscles was associated with higher ATP turnover rate and larger amounts of ATP consumed per contraction. Metabolic stress further aggravated the energetic cost in AK1−/− muscles. Thus, AK1‐catalyzed phosphotransfer is essential in the maintenance of cellular energetic economy, enabling skeletal muscle to perform at the lowest metabolic cost.