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ORIGINAL RESEARCH article

Front. Cell Dev. Biol.
Sec. Molecular and Cellular Reproduction
Volume 12 - 2024 | doi: 10.3389/fcell.2024.1431683

Decreased ATF5 level contributes to improved mitochondrial function in oocytes exposed to vitrification stress

Provisionally accepted
Guizhen Zhou Guizhen Zhou 1Jun Li Jun Li 2Aiju Liu Aiju Liu 1Jiachen Bai Jiachen Bai 1HongYu Liu HongYu Liu 1Yixiao Zhu Yixiao Zhu 1Yuwen Luo Yuwen Luo 1Lv Zheng Lv Zheng 1Yunpeng Hou Yunpeng Hou 1Xiangwei Fu Xiangwei Fu 1*
  • 1 China Agricultural University, Beijing, China
  • 2 The First Hospital of Hebei Medical University, Shijiazhuang, China

The final, formatted version of the article will be published soon.

    Mitochondrial unfolded protein response (mtUPR) plays an essential role in the response of mitochondria to stress-induced damage. Activating of transcription factor 5 (ATF5) can help to sustain mitochondrial function and regulate organelle recovery under mitochondrial stress. Vitrification is a stressor that disrupts mitochondrial activity and cell homeostasis. However, little is known about the function of ATF5 in response to the extreme biophysical and chemical stresses during oocyte vitrification. In the present study, the mitochondrial membrane potential and ATP levels were decreased in ATF5 knockdown oocytes, in line with the phenotypes observed in vitrified oocytes. In addition, ATF5 knockdown resulted in decreased mitochondrial temperature, reduced unfolded protein levels, abnormal mitochondrial dynamics (fusion and fission), and increased autophagy. Subsequent experiments indicated that mtUPR was suppressed in oocytes with ATF5 knockdown. Interestingly, ATF5 was aberrantly up-regulated in oocytes exposed to vitrification stress. Reduced ATF5 expression to a homeostatic level in vitrified oocytes led to accumulated unfolded protein levels and increased mitochondrial membrane potential. Moreover, increased mitochondrial dynamics and an increased germinal vescile breakdown (GVBD) rate were detected after in vitro maturation. Transcriptome analysis revealed that ATF5 is involved in the vitrification stress response, and ATF5 regulated the in vitro maturation potential in vitrified oocytes through the cAMP-PKA and PI3K/AKT pathways. In summary, our findings indicate that mtUPR was initiated in response to vitrification stimuli, and down-regulated ATF5 level to a homeostatic state contributes to improved mitochondrial function in oocytes exposed to vitrification stress. Our results highlight the crucial role of ATF5 in the regulation of mitochondrial function in vitrified oocytes through mediating mtUPR.

    Keywords: mitochondrial unfolded protein responses, ATF5, Mitochondrial dysfunction, Vitrification, oocytes Oxidoreductase activity Decr1, Cyp4a10, CBS, P4HA2

    Received: 12 May 2024; Accepted: 09 Sep 2024.

    Copyright: © 2024 Zhou, Li, Liu, Bai, Liu, Zhu, Luo, Zheng, Hou and Fu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Xiangwei Fu, China Agricultural University, Beijing, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.