Startseite Yeast Bxi1/Ybh3 mediates conserved mitophagy and apoptosis in yeast and mammalian cells: convergence in Bcl-2 family
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Yeast Bxi1/Ybh3 mediates conserved mitophagy and apoptosis in yeast and mammalian cells: convergence in Bcl-2 family

  • Yuying Wang , Zhiyuan Hu , Maojun Jiang , Yanxin Zhang , Linjie Yuan , Ziqian Wang , Ting Song EMAIL logo und Zhichao Zhang EMAIL logo
Veröffentlicht/Copyright: 12. März 2024

Abstract

The process of degrading unwanted or damaged mitochondria by autophagy, called mitophagy, is essential for mitochondrial quality control together with mitochondrial apoptosis. In mammalian cells, pan-Bcl-2 family members including conical Bcl-2 members and non-conical ones are involved in and govern the two processes. We have illustrated recently the BH3 receptor Hsp70 interacts with Bim to mediate both apoptosis and mitophagy. However, whether similar pathways exist in lower eukaryotes where conical Bcl-2 members are absent remained unclear. Here, a specific inhibitor of the Hsp70-Bim PPI, S1g-10 and its analogs were used as chemical tools to explore the role of yeast Bxi1/Ybh3 in regulating mitophagy and apoptosis. Using Om45-GFP processing assay, we illustrated that yeast Ybh3 mediates a ubiquitin-related mitophagy pathway in both yeast and mammalian cells through association with Hsp70, which is in the same manner with Bim. Moreover, by using Bax/Bak double knockout MEF cells, Ybh3 was identified to induce apoptosis through forming oligomerization to trigger mitochondrial outer membrane permeabilization (MOMP) like Bax. We not only illustrated a conserved ubiquitin-related mitophagy pathway in yeast but also revealed the multi-function of Ybh3 which combines the function of BH3-only protein and multi-domain Bax protein as one.


Corresponding authors: Ting Song and Zhichao Zhang, School of Chemistry, Dalian University of Technology, Dalian 116024, Liaoning, China, E-mail: (T. Song), (Z. Zhang)

Award Identifier / Grant number: 2022ZXYG46, DUT22YG106, DUT22YG223, DUT23YG125

Award Identifier / Grant number: 82073703, 82270186, 82273778

Acknowledgments

The authors thank Prof. Xinguang Liu (Guangdong Medical University) for the kind gift of yeast strains.

  1. Research ethics: Not applicable.

  2. Author contributions: Conceptualization, YW, TS, and ZZ; data curation, YW, TS, and ZZ; Yeast and Cell culture, Western blotting and co-immunoprecipitation, YW, ZH; fluorescence properties detection and apoptosis assay, YW and YL; chemical synthesis, MJ and ZW; size-exclusion chromatography analysis, YW and YZ; writing-original draft preparation, YW, TS and ZZ; Writing-review & editing, WY, TS and ZZ; funding acquisition, TS and ZZ. All the authors have read and agreed to the published version of the manuscript. All authors read and approved the final manuscript.

  3. Competing interests: The authors state no conflict of interest.

  4. Research funding: This research was supported by the National Natural Science Foundation of China (82270186, 82073703 and 82273778) and the Fundamental Research Funds for the Central University (DUT22YG223, DUT22YG106, DUT23YG125, and 2022ZXYG46).

  5. Data availability: The raw data can be obtained on request from the corresponding author.

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Received: 2023-12-01
Accepted: 2024-02-28
Published Online: 2024-03-12
Published in Print: 2024-06-25

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