TY - JOUR
T1 - Differing roles of pyruvate dehydrogenase kinases during mouse oocyte maturation
AU - Hou, Xiaojing
AU - Zhang, Liang
AU - Han, Longsen
AU - Ge, Juan
AU - Ma, Rujun
AU - Zhang, Xuesen
AU - Moley, Kelle
AU - Schedl, Tim
AU - Wang, Qiang
N1 - Publisher Copyright:
© 2015. Published by The Company of Biologists Ltd.
PY - 2015
Y1 - 2015
N2 - Pyruvate dehydrogenase kinases (PDKs) modulate energy homeostasis in multiple tissues and cell types, under various nutrient conditions, through phosphorylation of the α subunit (PDHE1α, also known as PDHA1) of the pyruvate dehydrogenase (PDH) complex. However, the roles of PDKs in meiotic maturation are currently unknown. Here, by undertaking knockdown and over expression analysis of PDK paralogs (PDK1-PDK4) in mouse oocytes, we established the site-specificity of PDKs towards 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 and PDK2 promote meiotic maturation, as their knockdown disturbs the assembly of the meiotic apparatus, without significantly altering ATP content. Moreover, phosphorylation of Ser232-PDHE1α was demonstrated to mediate PDK1 and PDK2 action in meiotic maturation, possibly through a mechanism that is distinct from PDH inactivation. These findings reveal that there are divergent roles of PDKs during oocyte maturation and indicate a new mechanism controlling meiotic structure.
AB - Pyruvate dehydrogenase kinases (PDKs) modulate energy homeostasis in multiple tissues and cell types, under various nutrient conditions, through phosphorylation of the α subunit (PDHE1α, also known as PDHA1) of the pyruvate dehydrogenase (PDH) complex. However, the roles of PDKs in meiotic maturation are currently unknown. Here, by undertaking knockdown and over expression analysis of PDK paralogs (PDK1-PDK4) in mouse oocytes, we established the site-specificity of PDKs towards 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 and PDK2 promote meiotic maturation, as their knockdown disturbs the assembly of the meiotic apparatus, without significantly altering ATP content. Moreover, phosphorylation of Ser232-PDHE1α was demonstrated to mediate PDK1 and PDK2 action in meiotic maturation, possibly through a mechanism that is distinct from PDH inactivation. These findings reveal that there are divergent roles of PDKs during oocyte maturation and indicate a new mechanism controlling meiotic structure.
KW - Meiosis
KW - Metabolism
KW - Oocyte
KW - Pyruvate dehydrogenase kinase
KW - Spindle
UR - http://www.scopus.com/inward/record.url?scp=84935496419&partnerID=8YFLogxK
U2 - 10.1242/jcs.167049
DO - 10.1242/jcs.167049
M3 - Article
C2 - 25991547
AN - SCOPUS:84935496419
SN - 0021-9533
VL - 128
SP - 2319
EP - 2329
JO - Journal of cell science
JF - Journal of cell science
IS - 13
ER -