Article

Mitochondrial proteome of mouse oocytes and cisplatin- induced shifts in protein profile

Na Zhang1,2,3,4, An-di Sun1,2,3,4, Si-man Sun1, Rui Yang1,2, Yan-yan Shi5, Qi-long Wang1,3, Xin-yu Li1,3, Ji-hong Ma1, Wei Yue1, Bing-teng Xie1,2,3, Jie Qiao1,2,3,4, Mo Li1,2,3,4
1 Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing 100191, China
2 National Clinical Research Center for Obstetrics and Gynecology (Peking University Third Hospital), Beijing 100191, China
3 Key Laboratory of Assisted Reproduction (Peking University), Ministry of Education, Beijing 100191, China
4 Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology, Beijing 100191, China
5 Research Center of Clinical Epidemiology, Peking University Third Hospital, Beijing 100191, China
Correspondence to: Bing-teng Xie: xiebingteng@bjmu.edu.cn, Mo Li: limo@hsc.pku.edu.cn,
DOI: 10.1038/s41401-021-00687-4
Received: 19 January 2021
Accepted: 24 April 2021
Advance online: 20 May 2021

Abstract

Mitochondria are essential organelles that provide energy for mammalian cells and participate in multiple functions, such as signal transduction, cellular differentiation, and regulation of apoptosis. Compared with the mitochondria in somatic cells, oocyte mitochondria have an additional level of importance since they are required for germ cell maturation, dysfunction in which can lead to severe inherited disorders. Thus, a systematic proteomic profile of oocyte mitochondria is urgently needed to support the basic and clinical research, but the acquisition of such a profile has been hindered by the rarity of oocyte samples and technical challenges associated with capturing mitochondrial proteins from live oocytes. Here, in this work, using proximity labeling proteomics, we established a mitochondria-specific ascorbate peroxidase (APEX2) reaction in live GV-stage mouse oocytes and identified a total of 158 proteins in oocyte mitochondria. This proteome includes intrinsic mitochondrial structural and functional components involved in processes associated with “cellular respiration”, “ATP metabolism”, “mitochondrial transport”, etc. In addition, mitochondrial proteome capture after oocyte exposure to the antitumor chemotherapeutic cisplatin revealed differential changes in the abundance of several oocyte-specific mitochondrial proteins. Our study provides the first description of a mammalian oocyte mitochondrial proteome of which we are aware, and further illustrates the dynamic shifts in protein abundance associated with chemotherapeutic agents.
Keywords: mitochondrial proteome; APEX2; proximity labeling; mouse oocyte; cisplatin

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