VPS34 governs oocyte developmental competence by regulating mito-autophagy-a novel insight into the significance of Rab7 activity and its subcellular location.
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Title of Paper:VPS34 governs oocyte developmental competence by regulating mito-autophagy-a novel insight into the significance of Rab7 activity and its subcellular location. Journal:Advanced Science Place of Publication:USA Key Words:autophagy,mitophagy,oocyte,retromer,VPS34 Summary:Asynchronous nuclear and cytoplasmic maturation in human oocytes is believed to cause morphological anomalies after controlled ovarian hyperstimulation. Vacuolar protein sorting 34 (VPS34) is renowned for its pivotal role in regulating autophagy and endocytic trafficking. To investigate its impact on oocyte development, oocyte‐specific knockout mice (ZcKO) are generated, and these mice are completely found infertile, with embryonic development halted at 2‐ to 4‐cell stage. This infertility is related with a disruption on autophagic/mitophagic flux in ZcKO oocytes, leading to subsequent failure of zygotic genome activation (ZGA) in derived 2‐cell embryos. The findings further elucidated the regulation of VPS34 on the activity and subcellular translocation of RAS‐related GTP‐binding protein 7 (RAB7), which is critical not only for the maturation of late endosomes and lysosomes, but also for initiating mitophagy via retrograde trafficking. VPS34 binds directly with RAB7 and facilitates its activity conversion through TBC1 domain family member 5 (TBC1D5). Consistent with the cytoplasmic vacuolation observed in ZcKO oocytes, defects in multiple vesicle trafficking systems are also identified in vacuolated human oocytes. Furthermore, activating VPS34 with corynoxin B (CB) treatment improved oocyte quality in aged mice. Hence, VPS34 activation may represent a novel approach to enhance oocyte quality in human artificial reproduction. First Author:Wenwen Liu Correspondence Author:Jing Li,Feiyang Diao,Wenpei Xiang All the Authors:Qingyuan Sun,Youqiang Su,Shiming Luo,Xiaowei Dou,Yan Sun,Ling Zhang,Wenya Sun,Yuexin Qiu,Xin Jin,Lu Wang,Yuting Lin,Kehan Wang Document Code:10.1002/advs.202308823 Volume:11 Issue:41 Page Number:e2308823 ISSN:2198-3844 Translation or Not:No Date of Publication:2024-09 Release Time:2025-04-30
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