Perturbations in energy metabolism cause meiotic defects in mammalian oocytes. It has been suggested that these may be exerted through pyruvate dehydrogenase kinases (PDKs) that act on the pyruvate dehydrogenase complex (PDH), which, in somatic cells, is inhibited by phosphorylation of its catalytic subunit PDHE1α at serine residues S232, S292 and S300; however, the role of particular PDKs in the maturation of meiotic oocytes is still unclear. Qiang Wang and colleagues (p. ), therefore, examined the individual contributions of known mammalian PDKs to the regulation of murine oocyte maturation. They found that oocytes that overexpress PDK3 have elevated levels of PDHE1α phosphorylated at S293, defects in polar body 1 (Pb1) extrusion, as well as a disorganised spindle and misaligned chromosomes. Moreover, in keeping with a central role of PDH in energy production, the authors also found decreased levels of ATP. These spindle and chromosome abnormalities, as well as metabolic defects could be rescued with a phosphorylation resistant PDH-S293A mutant. By contrast, knockdown of PDK1 or PDK2, both of which phosphorylate S232, caused defects in Pb1 extrusion, spindle assembly and chromosome alignment, but did not affect the level of total ATP. Taken together, these results reveal that PDK3-dependent phosphorylation of PDHE1α at S293 affects oocyte maturation through PDH inhibition and changes in metabolism, whereas PDK1/PDK2-mediated PDHE1α phosphorylation at S232 has effects on oocyte meiosis that may be independent of PDH's role in energy production.
