NDLI: Differing roles of pyruvate dehydrogenase kinases during mouse oocyte maturation

Content Provider	PubMed Central
Author	Hou, Xiaojing Zhang, Liang Han, Longsen Juan, Ge Ma, Rujun Zhang, Xuesen Moley, Kelle Schedl, Tim Wang, Qiang
Copyright Year	2015
Abstract	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 overexpression 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.
Related Links	http://dx.doi.org/10.1242/jcs.167049
Ending Page	2329
Page Count	11
Starting Page	2319
File Format	PDF
ISSN	00219533
e-ISSN	14779137
Journal	Journal of Cell Science
Issue Number	13
Volume Number	128
Language	English
Publisher	The Company of Biologists
Publisher Date	2015-07-01
Access Restriction	Open
Rights Holder	The Company of Biologists
Subject Keyword	Cell Biology Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Cell Biology

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4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
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