SIRT 4 is essential for metabolic control and meiotic structure during mouse oocyte maturation
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 c...
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Veröffentlicht in: | Aging cell 2018-08, Vol.17 (4) |
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Hauptverfasser: | , , , , , , , , , , , , |
Format: | Artikel |
Sprache: | eng |
Online-Zugang: | Volltext |
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Zusammenfassung: | 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. |
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ISSN: | 1474-9718 1474-9726 |
DOI: | 10.1111/acel.12789 |