Selective autophagic degradation of ACLY (ATP citrate lyase) maintains citrate homeostasis and promotes oocyte maturation

自噬 ATP柠檬酸裂解酶 卵母细胞 生物 细胞生物学 柠檬酸合酶 卵泡发生 卵泡液 内分泌学 生物化学 细胞凋亡 胚胎 低温保存
作者
Hainan He,Junling Wang,Xingmei Mou,Xin Liu,Qiao Li,Mingyue Zhong,Bingbing Luo,Zhisheng Yu,Jingjing Zhang,Tian Xu,Chengli Dou,Dan‐Ya Wu,Wei Qing,Linhui Wu,Zongke Zhou,Zhengang Fan,Tingting Wang,Taotao Hu,Xia Zhang,Jilong Zhou,Yi‐Liang Miao
出处
期刊:Autophagy [Informa]
卷期号:19 (1): 163-179 被引量:18
标识
DOI:10.1080/15548627.2022.2063005
摘要

ABSTRACTMacroautophagy/autophagy is a cellular and energy homeostatic mechanism that contributes to maintain the number of primordial follicles, germ cell survival, and anti-ovarian aging. However, it remains unknown whether autophagy in granulosa cells affects oocyte maturation. Here, we show a clear tendency of reduced autophagy level in human granulosa cells from women of advanced maternal age, implying a potential negative correlation between autophagy levels and oocyte quality. We therefore established a co-culture system and show that either pharmacological inhibition or genetic ablation of autophagy in granulosa cells negatively affect oocyte quality and fertilization ability. Moreover, our metabolomics analysis indicates that the adverse impact of autophagy impairment on oocyte quality is mediated by downregulated citrate levels, while exogenous supplementation of citrate can significantly restore the oocyte maturation. Mechanistically, we found that ACLY (ATP citrate lyase), which is a crucial enzyme catalyzing the cleavage of citrate, was preferentially associated with K63-linked ubiquitin chains and recognized by the autophagy receptor protein SQSTM1/p62 for selective autophagic degradation. In human follicles, the autophagy level in granulosa cells was downregulated with maternal aging, accompanied by decreased citrate in the follicular fluid, implying a potential correlation between citrate metabolism and oocyte quality. We also show that elevated citrate levels in porcine follicular fluid promote oocyte maturation. Collectively, our data reveal that autophagy in granulosa cells is a beneficial mechanism to maintain a certain degree of citrate by selectively targeting ACLY during oocyte maturation.Abbreviations: 3-MA: 3-methyladenine; ACLY: ATP citrate lyase; AMA: advanced maternal age; CG: cortical granule; CHX: cycloheximide; CQ: chloroquine; CS: citrate synthase; COCs: cumulus-oocyte-complexes; GCM: granulosa cell monolayer; GV: germinal vesicle; MII: metaphase II stage of meiosis; PB1: first polar body; ROS: reactive oxygen species; shRNA: small hairpin RNA; SQSTM1/p62: sequestosome 1; TCA: tricarboxylic acid; TOMM20/TOM20: translocase of outer mitochondrial membrane 20; UBA: ubiquitin-associated domain; Ub: ubiquitin; WT: wild-typeKEYWORDS: ACLYcitrateoocyte maturationselective autophagySQSTM1/p62 AcknowledgmentsWe thank Dr. Heide Schatten (University of Missouri) for helping us to improve our English language. We are grateful to Fangke Wang for her assistance in the pattern diagram drawing.Data availabilityAll sequencing data related to this study have been deposited at Gene Expression Omnibus (GEO, https://www.ncbi.nlm.nih.gov/geo/) under the accession number GSE190697.Disclosure statementNo potential conflict of interest was reported by the author(s).Supplementary materialSupplemental data for this article can be accessed here.Additional informationFundingThis work was supported by the National Natural Science Foundation of China (Grant# 31801242), Key Research and Development Program of Hubei Province (Grant# 2021BBA221), the project supported by the Fundamental Research Funds for the Central University (Grant# 2662020DKQD001), Hubei Province Science and Technology Basic Conditions Platform (2020DFE020).
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
大幅提高文件上传限制,最高150M (2024-4-1)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
1秒前
潇洒自由基完成签到 ,获得积分10
2秒前
Dusk大寺柯完成签到,获得积分10
3秒前
徐徐徐应助李大龙采纳,获得10
4秒前
zky发布了新的文献求助10
4秒前
whtestar完成签到,获得积分10
4秒前
Ry驳回了打打应助
5秒前
5秒前
peach完成签到,获得积分10
6秒前
nimo完成签到 ,获得积分10
6秒前
6秒前
7秒前
稳重的汉堡完成签到,获得积分10
7秒前
ming完成签到,获得积分10
7秒前
ZQ完成签到,获得积分10
8秒前
123完成签到,获得积分20
8秒前
靓丽访枫发布了新的文献求助10
8秒前
动听的谷秋完成签到 ,获得积分10
8秒前
可爱的函函应助桑梓采纳,获得10
9秒前
大气的玉米完成签到,获得积分10
9秒前
SongWhizz完成签到,获得积分20
9秒前
bigpluto完成签到,获得积分10
9秒前
潇洒绿蕊完成签到,获得积分10
9秒前
沙漏完成签到,获得积分10
10秒前
10秒前
10秒前
筑梦之鱼完成签到,获得积分10
10秒前
虚拟的函发布了新的文献求助10
10秒前
luyang完成签到,获得积分10
10秒前
linxue完成签到 ,获得积分10
11秒前
小树林发布了新的文献求助10
11秒前
11秒前
小小完成签到 ,获得积分10
11秒前
北林发布了新的文献求助10
12秒前
微微完成签到,获得积分10
12秒前
12秒前
13秒前
13秒前
Allot完成签到,获得积分10
13秒前
sci01完成签到 ,获得积分10
13秒前
高分求助中
Sustainability in Tides Chemistry 2800
The Young builders of New china : the visit of the delegation of the WFDY to the Chinese People's Republic 1000
Rechtsphilosophie 1000
Bayesian Models of Cognition:Reverse Engineering the Mind 888
Le dégorgement réflexe des Acridiens 800
Defense against predation 800
A Dissection Guide & Atlas to the Rabbit 600
热门求助领域 (近24小时)
化学 医学 生物 材料科学 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 基因 遗传学 催化作用 物理化学 免疫学 量子力学 细胞生物学
热门帖子
关注 科研通微信公众号,转发送积分 3134291
求助须知:如何正确求助?哪些是违规求助? 2785137
关于积分的说明 7770495
捐赠科研通 2440760
什么是DOI,文献DOI怎么找? 1297506
科研通“疑难数据库(出版商)”最低求助积分说明 624987
版权声明 600792