<scp>SIRT</scp>4 is essential for metabolic control and meiotic structure during mouse oocyte maturation

Abstract

Abstract SIRT 4 modulates energy homeostasis in multiple cell types and tissues. However, its role in meiotic oocytes remains unknown. Here, we report that mouse oocytes overexpressing SIRT 4 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‐ PDHE 1α mediates the effects of SIRT 4 overexpression on metabolic activity and meiotic events in oocytes by performing functional rescue experiments. By chance, we discover the SIRT 4 upregulation in oocytes from aged mice; and importantly, the maternal age‐associated deficient phenotypes in oocytes can be partly rescued through the knockdown of SIRT 4. These findings reveal the critical role for SIRT 4 in the control of energy metabolism and meiotic apparatus during oocyte maturation and indicate that SIRT 4 is an essential factor determining oocyte quality.