The adenosine salvage pathway as an alternative to mitochondrial production of ATP in maturing mammalian oocytes

Mitochondria in maturing oocytes and early embryos change shape from the usual mature form seen in other cells to an immature form that has very limited capacity for energy production from glucose and oxidative phosphorylation (OXPHOS). With the high demand for energy in these cells and limited capacity for OXPHOS, it is unclear how these cells meet their energy needs. This study provides evidence that a previously unexplored potential driver of ATP synthesis, the adenosine salvage pathway, can meet the energy needs of growing bovine oocytes. Considerable amounts of adenosine monophosphate (AMP) become available at the onset of maturation trough the destruction of cyclic AMP by phosphodiesterases which triggers resumption of meiosis. The conversion of AMP to ADP and then to ATP occurs through the action of 2 enzymes. The first of these, adenylate kinase, catalyzes the conversion of AMP to ADP; the second, creatine kinase, converts ADP to ATP. Adding inhibitors of these enzymes to the oocyte maturation medium decreased ATP production; adding their substrates to denuded oocytes restored ATP production. Adding phosphocreatine alone also restored ATP levels substantially and influenced the phenotype of the resulting blastocysts, improving embryo quality and yield. The use of the adenosine salvage pathway explains how growing oocytes with limited ability to generate ATP through traditional OXPHOS pathways can meet energy requirements.