VPS34 Governs Oocyte Developmental Competence by Regulating Mito/Autophagy: A Novel Insight into the Significance of RAB7 Activity and Its Subcellular Location

被引：1

作者：

Liu, Wenwen ^{[1
]}

Wang, Kehan ^{[2
]}

Lin, Yuting ^{[3
]}

Wang, Lu ^{[4
,5
]}

Jin, Xin ^{[4
,6
]}

Qiu, Yuexin ^{[4
]}

Sun, Wenya ^{[4
]}

Zhang, Ling ^{[7
]}

Sun, Yan ^{[4
]}

Dou, Xiaowei ^{[4
,8
]}

Luo, Shiming ^{[9
]}

Su, Youqiang ^{[10
]}

Sun, Qingyuan ^{[9
]}

Xiang, Wenpei ^{[7
]}

Diao, Feiyang ^{[3
]}

Li, Jing ^{[4
,11
]}

机构：

[1] Nanjing Med Univ, Womens Hosp, Nanjing Matern & Child Hlth Care Hosp, State Key Lab Reprod Med & Offspring Hlth, Nanjing 211166, Jiangsu, Peoples R China

[2] Nanjing Med Univ, Suzhou Municipal Hosp, State Key Lab Reprod Med & Offspring Hlth, Gusu Sch,Ctr Reprod & Genet,Affiliated Suzhou Hosp, Suzhou 215002, Jiangsu, Peoples R China

[3] Nanjing Med Univ, Ctr Clin Reprod Med, State Key Lab Reprod Med & Offspring Hlth, Affiliated Hosp 1, Nanjing 212028, Jiangsu, Peoples R China

[4] Nanjing Med Univ, State Key Lab Reprod Med & Offspring Hlth, Nanjing 211166, Jiangsu, Peoples R China

[5] Cangzhou Cent Hosp, Dept Reprod Med, Cangzhou 061012, Hebei, Peoples R China

[6] Nanjing Med Univ, Wuxi Matern & Child Hlth Care Hosp, Dept Ctr Reprod Med, Wuxi 214200, Jiangsu, Peoples R China

[7] Huazhong Univ Sci & Technol, Inst Reprod Hlth, Tongji Med Coll, Wuhan 430074, Hubei, Peoples R China

[8] Nanjing Med Univ, Affiliated Hosp 2, Dept Obstet & Gynecol, Nanjing 210011, Jiangsu, Peoples R China

[9] Guangdong Second Prov Gen Hosp, Reprod Med Ctr, Guangzhou Key Lab Metab Dis & Reprod Hlth, Guangdong Hong Kong Metab & Reprod Joint Lab, Guangzhou 513023, Guangdong, Peoples R China

[10] Shandong Univ, Sch Life Sci, Shandong Prov Key Lab Anim Cells & Dev Biol, Qingdao 266237, Shandong, Peoples R China

[11] Suzhou Nanjing Med Univ, Innovat Ctr, Suzhou 430074, Peoples R China

来源：

ADVANCED SCIENCE | 2024年 / 11卷 / 41期

基金：

中国国家自然科学基金;

关键词：

autophagy; mitophagy; oocyte; retromer; VPS34; AUTOPHAGY; TRAFFICKING; ROLES; ENDOCYTOSIS; RECRUITMENT; MECHANISMS; MORPHOLOGY; EXPRESSION; MATURATION; DELETION;

D O I：

10.1002/advs.202308823

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

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.

引用

页数：22