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刘鑫

博士生导师
硕士生导师
教师姓名:刘鑫
教师拼音名称:Liu Xin
电子邮箱:
办公地点:第四综合楼E615
职称:副研究员
毕业院校:西北农林科技大学
所属院系:动物科学技术学院、动物医学院
学科:动物遗传育种与繁殖    
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论文成果
Selective autophagic degradation of ACLY (ATP citrate lyase) maintains citrate homeostasis and promotes oocyte maturation
发布时间:2022-07-24    点击次数:

影响因子:16.016

DOI码:10.1080/15548627.2022.2063005.

发表刊物:Autophagy (B刊)

摘要:Macroautophagy/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.

合写作者:Mou XM,Liu X,Li Q,Zhong MY,Luo BB,Yu ZS,Zhang JJ,Xu T,Dou CL,Wu DY,Qin W,Wu LH,Zhou K,Fan ZG,Wang TT,Hu TT,Zhang X

第一作者:He HN#,Wang JL#

论文类型:期刊论文

通讯作者:Zhou JL*,Miao YL*

卷号:Online

页面范围:1-17

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发表时间:2022-04-25

收录刊物:SCI

发布期刊链接:https://www.tandfonline.com/doi/full/10.1080/15548627.2022.2063005