Journal
AGING CELL
Volume 17, Issue 4, Pages -Publisher
WILEY
DOI: 10.1111/acel.12789
Keywords
aging; meiosis; metabolism; oocyte; SIRT4
Categories
Funding
- National Key RD Program [2017YFC1001500]
- National Natural Science Foundation [31571543, 31771657, 31601202, 81471429, 81730041]
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SIRT4 modulates energy homeostasis in multiple cell types and tissues. However, its role in meiotic oocytes remains unknown. Here, we report that mouse oocytes overexpressing SIRT4 are unable to completely progress through meiosis, showing the inadequate mitochondrial redistribution, lowered ATP content, elevated reactive oxygen species (ROS) level, with the severely disrupted spindle/chromosome organization. Moreover, we find that phosphorylation of Ser293-PDHE1 mediates the effects of SIRT4 overexpression on metabolic activity and meiotic events in oocytes by performing functional rescue experiments. By chance, we discover the SIRT4 upregulation in oocytes from aged mice; and importantly, the maternal age-associated deficient phenotypes in oocytes can be partly rescued through the knockdown of SIRT4. These findings reveal the critical role for SIRT4 in the control of energy metabolism and meiotic apparatus during oocyte maturation and indicate that SIRT4 is an essential factor determining oocyte quality.
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