Molecules and Cells

Korean Society for Molecular and Cellular Biology (한국분자세포생물학회)
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Suboptimal Mitochondrial Activity Facilitates Nuclear Heat Shock Responses for Proteostasis and Genome Stability

  • Dongkeun Park (Department of Biological Sciences, Ulsan National Institute of Science and Technology (UNIST)) ;
  • Youngim Yu (Department of Biological Sciences, Ulsan National Institute of Science and Technology (UNIST)) ;
  • Ji-hyung Kim (Department of Biological Sciences, Ulsan National Institute of Science and Technology (UNIST)) ;
  • Jongbin Lee (Department of Biological Sciences, Ulsan National Institute of Science and Technology (UNIST)) ;
  • Jongmin Park (Department of Biological Sciences, Ulsan National Institute of Science and Technology (UNIST)) ;
  • Kido Hong (Department of Biological Sciences, Ulsan National Institute of Science and Technology (UNIST)) ;
  • Jeong-Kon Seo (UNIST Central Research Facilities (UCRF), Ulsan National Institute of Science and Technology) ;
  • Chunghun Lim (Department of Biological Sciences, Ulsan National Institute of Science and Technology (UNIST)) ;
  • Kyung-Tai Min (Department of Biological Sciences, Ulsan National Institute of Science and Technology (UNIST))
  • Received : 2022.11.21
  • Accepted : 2023.01.17
  • Published : 2023.06.30
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Abstract

Thermal stress induces dynamic changes in nuclear proteins and relevant physiology as a part of the heat shock response (HSR). However, how the nuclear HSR is fine-tuned for cellular homeostasis remains elusive. Here, we show that mitochondrial activity plays an important role in nuclear proteostasis and genome stability through two distinct HSR pathways. Mitochondrial ribosomal protein (MRP) depletion enhanced the nucleolar granule formation of HSP70 and ubiquitin during HSR while facilitating the recovery of damaged nuclear proteins and impaired nucleocytoplasmic transport. Treatment of the mitochondrial proton gradient uncoupler masked MRP-depletion effects, implicating oxidative phosphorylation in these nuclear HSRs. On the other hand, MRP depletion and a reactive oxygen species (ROS) scavenger non-additively decreased mitochondrial ROS generation during HSR, thereby protecting the nuclear genome from DNA damage. These results suggest that suboptimal mitochondrial activity sustains nuclear homeostasis under cellular stress, providing plausible evidence for optimal endosymbiotic evolution via mitochondria-to-nuclear communication.

Keywords

Acknowledgement

We thank Franz-Ulrich Hartl, Jeffrey Rothstein, Addgene, and Developmental Studies Hybridoma Bank for reagents. This work was supported by grants from the Suh Kyungbae Foundation (SUHF-17020101); from the National Research Foundation funded by the Ministry of Science and Information & Communication Technology (MSIT), Republic of Korea (NRF-2021R1A2C3011706; NRF-2021M3A9G8022960; NRF-2018R1A5A1024261).

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