NCBI Summary:
The pyruvate dehydrogenase (PDH) complex is a nuclear-encoded mitochondrial multienzyme complex that catalyzes the overall conversion of pyruvate to acetyl-CoA and CO(2), and provides the primary link between glycolysis and the tricarboxylic acid (TCA) cycle. The PDH complex is composed of multiple copies of three enzymatic components: pyruvate dehydrogenase (E1), dihydrolipoamide acetyltransferase (E2) and lipoamide dehydrogenase (E3). The E1 enzyme is a heterotetramer of two alpha and two beta subunits. This gene encodes the E1 alpha 1 subunit containing the E1 active site, and plays a key role in the function of the PDH complex. Mutations in this gene are associated with pyruvate dehydrogenase E1-alpha deficiency and X-linked Leigh syndrome. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Mar 2010]
General function
Enzyme
Comment
Cellular localization
Cytoplasmic, Mitochondrial
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Ovarian function
Oocyte maturation
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Differential function of pyruvate dehydrogenase kinases during mouse oocyte maturation. Hou X et al. (2015) Pyruvate dehydrogenase kinases (PDKs) modulate energy homeostasis in multiple tissues/cell types, under various nutrient conditions, through phosphorylation of the α subunit (PDHE1α) of the pyruvate dehydrogenase (PDH) complex. However, the roles of PDKs in meiotic maturation are currently unknown. Here, by employing morpholino knockdown and overexpression analysis of PDK paralogs (PDK1-4) in mouse oocytes, we established the site-specificity of PDKs toward the phosphorylation of three serine residues (Ser232, Ser293 and Ser300) on PDHE1α. We found that PDK3-mediated phosphorylation of Ser293-PDHE1α results in disruption of meiotic spindle morphology and chromosome alignment and decreased total ATP levels, probably through inhibition of PDH activity. Unexpectedly, we discovered that PDK1/2 promote meiotic maturation as their knockdown disturbs the assembly of meiotic apparatus, without significantly altered ATP content. Moreover, phosphorylation of Ser232-PDHE1α was demonstrated to mediate PDK1/2 action in meiotic maturation, possibly through a mechanism that is distinct from PDH inactivation. These findings reveal divergent roles of PDKs during oocyte maturation and indicate a novel mechanism controlling meiotic structure.//////////////////