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Heat shock transcriptional factor mediates mitochondrial unfolded protein response

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Abstract

For maintenance of cytoplasmic protein quality control (PQC), cytoplasmic heat shock proteins (HSPs) negatively control heat shock transcriptional factor (HSF) in a negative feedback loop. However, how mitochondrial protein quality control (mtPQC) is maintained is largely unknown. Here we present evidence that HSF directly monitors mtPQC in the budding yeast Saccharomyces cerevisiae. Mitochondrial HSP70 (Ssc1) negatively regulated HSF activity. Importantly, HSF was localized not only in the nucleus but also on mitochondria. The mitochondrial localization of HSF was increased by heat shock and compromised by SSC1 overexpression. Furthermore, the mitochondrial protein translocation system downregulated HSF activity. Finally, mtPQC modulated the mtHSP genes SSC1 and MDJ1 via HSF, and SSC1 overexpression compromised mitochondrial function. These findings illustrate a model in which HSF directly monitors mtPQC.

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Acknowledgements

We thank Toshiya Endo, Walter Neupert, Sabine Rospert, Bent Jakobsen, Dennis Winge, Kazutoshi Mori, Shuh-ichi Nishikawa, Takehiko Shibata, Markus Proft, Ramón Serrano, and Koji Okamoto for generous gifts of materials. We especially thank Tomohusa Tachibana and Yoshihiro Kato for execution of preliminary experiments. We give special thanks to Toshiya Endo and Shuh-ichi Nishikawa, and laboratory members of TU for helpful discussions. BY4741 was provided by the National Bio-Resource Project (NBRP) of the MEXT, Japan.

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Authors and Affiliations

  1. Graduate School of Science and Technology, Shizuoka University, Ohya 836, Suruga-ku, Shizuoka, 422-8021, Japan

    Naoki Koike & Takashi Ushimaru

  2. Faculty of Science, Shizuoka University, 836 Ohya, Shizuoka, 422-8529, Japan

    Yuuki Hatano & Takashi Ushimaru

Authors
  1. Naoki Koike
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  2. Yuuki Hatano
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  3. Takashi Ushimaru
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Contributions

TU conceived and initiated the project. TU designed the experiments. NK, YH, and TU executed the experiments and analyzed the data. NK, YH, and TU discussed the data. TU wrote the paper.

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Correspondence to Takashi Ushimaru.

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No potential conflicts of interest were disclosed.

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Communicated by M. Kupiec.

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Koike, N., Hatano, Y. & Ushimaru, T. Heat shock transcriptional factor mediates mitochondrial unfolded protein response. Curr Genet 64, 907–917 (2018). https://doi.org/10.1007/s00294-018-0809-9

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  • DOI: https://doi.org/10.1007/s00294-018-0809-9

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