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HIGH STEROL ESTER 1 is a key factor in plant sterol homeostasis

Nature Plants volume 5, pages 1154–1166 (2019)Cite this article

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Abstract

Plants strictly regulate the levels of sterol in their cells, as high sterol levels are toxic. However, how plants achieve sterol homeostasis is not fully understood. We isolated an Arabidopsis thaliana mutant that abundantly accumulated sterol esters in structures of about 1 µm in diameter in leaf cells. We designated the mutant high sterol ester 1 (hise1) and called the structures sterol ester bodies. Here, we show that HISE1, the gene product that is altered in this mutant, functions as a key factor in plant sterol homeostasis on the endoplasmic reticulum (ER) and participates in a fail-safe regulatory system comprising two processes. First, HISE1 downregulates the protein levels of the β-hydroxy β-methylglutaryl-CoA reductases HMGR1 and HMGR2, which are rate-limiting enzymes in the sterol synthesis pathway, resulting in suppression of sterol overproduction. Second, if the first process is not successful, excess sterols are converted to sterol esters by phospholipid sterol acyltransferase1 (PSAT1) on ER microdomains and then segregated in SE bodies.

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Fig. 1: The A. thaliana mutant hise1 abnormally develops lipophilic structures.
Fig. 2: hise1 mutants accumulate much higher levels of sterol esters in SE bodies.
Fig. 3: Hyperaccumulation of HMGR proteins in hise1 mutant.
Fig. 4: hise1 mutant has dramatically higher sterol-producing activity than the wild type.
Fig. 5: Deficiency of PSAT1 causes defects in SE-body formation and plant growth of hise1.
Fig. 6: HISE1 localizes to the ER whereas PSAT1 localizes to ER microdomains.
Fig. 7: A hypothetical model of a HISE1-dependent failsafe regulatory system for sterol homeostasis via HMGR downregulation.

Data availability

Sequence data from this study can be found in the GenBank/EMBL data libraries under the following accession numbers: CLO3 (At2g33380, NM_128898), HISE1 (At1g60995, NM_001084280), PSAT1 (At1g04010, NM_100282), HMGR1 (At1g76490, NM_106299), HMGR2 (At2g17370, NM_127292) and EF1a (At5g60390, NM_125432). The data that support the findings of this study are available from the corresponding author on request.

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Acknowledgements

We thank T. Nakagawa (Shimane University), S. Ishiguro (Nagoya University), M. Kaido (Kyoto University), T. Uemura (University of Tokyo), A. Nebenführ (University of Tennessee), E. Ito (International Christian University), K. Ebine (National Institute for Basic Biology), T. Goh (Nara Institute of Science and Technology) and Plant System Biology (VIB) for their donations of the vectors; S. Arai (Ochanomizu University), R. Iwahori (Ochanomizu University) and K. Takano (RIKEN Center for Sustainable Resource Science) for their technical assistance; the Arabidopsis Biological Resource Center for providing seeds of A. thaliana T-DNA insertion mutants; the Model Plant Research Facility (NIBB BioResource Center) and the Japan Advanced Plant Science Network (RIKEN) for their technical support; T. Muranaka (Osaka University) for the HMG1cd antibody; M. Hanaoka (Chiba University) for real-time PCR analysis; and J. Raymond (Eigoken) for critical readings of this manuscript. This work was supported by Grants-in-Aid for Scientific Research to I.H.-N. (no. 15H05776 and 22000014) and to T.L.S. (no. 16K18834 and 19K05809) from the Japan Society for the Promotion of Science (JSPS), by Leading Initiative for Excellent Young Researchers (LEADER) to T.L.S. (no. J16HJ00026) from the Ministry of Education, Culture, Sports, Science and Technology in Japan (MEXT), by SUNBOR GRANT of Suntory Foundation for life science to T.L.S., by Kato Memorial Bioscience Foundation to T.L.S., by Phytochemical Plant Molecular Science of Strategic Priority Research Promotion Program to T.L.S. and K.S. from Chiba University, and by the Hirao Taro Foundation of KONAN GAKUEN for Academic Research to I.H.-N.

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Authors and Affiliations

  1. Graduate School of Science, Kyoto University, Kyoto, Japan

    Takashi L. Shimada, Tomoo Shimada & Ikuko Hara-Nishimura

  2. Graduate School of Agriculture, Kyoto University, Kyoto, Japan

    Takashi L. Shimada & Yoshitaka Takano

  3. Graduate School of Science, The University of Tokyo, Tokyo, Japan

    Takashi L. Shimada & Akihiko Nakano

  4. Division of Cellular Dynamics, National Institute for Basic Biology, Okazaki, Japan

    Takashi L. Shimada & Takashi Ueda

  5. Graduate School of Horticulture, Chiba University, Matsudo, Japan

    Takashi L. Shimada

  6. RIKEN Center for Sustainable Resource Science, Yokohama, Japan

    Yozo Okazaki, Yasuhiro Higashi & Kazuki Saito

  7. Graduate School of Bioresources, Mie University, Tsu, Japan

    Yozo Okazaki

  8. Graduate School of Pharmaceutical Sciences, Chiba University, Chiba, Japan

    Kazuki Saito

  9. Institute of Transformative Bio-Molecules, Nagoya University, Nagoya, Japan

    Keiko Kuwata

  10. Graduate School of Humanities and Sciences, Ochanomizu University, Tokyo, Japan

    Kaori Oyama & Misako Kato

  11. Faculty of Science and Engineering, Konan University, Kobe, Japan

    Haruko Ueda & Ikuko Hara-Nishimura

  12. RIKEN Center for Advanced Photonics, Wako, Japan

    Akihiko Nakano

  13. JST, PRESTO, Kawaguchi, Japan

    Takashi Ueda

  14. SOKENDAI (Graduate University for Advanced Studies), Okazaki, Japan

    Takashi Ueda

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  1. Takashi L. Shimada
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Contributions

T.L.S., T.S. and I.H.-N. designed the research. T.L.S. performed the experiments, except for lipidome, proteome and radiolabelling experiments. Y.O., Y.H. and K.S. performed lipidome experiments, K.K. performed proteome experiments, and K.O. and M.K. performed in vivo- and in vitro-radiolabelling experiments. H.U. contributed to cell biological analysis and A.N., T.U. and Y.T. contributed to discussions. T.L.S. and I.H.-N. analysed the data and wrote the manuscript.

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Correspondence to Ikuko Hara-Nishimura.

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Peer review information Nature Plants thanks Narciso Campos, Hubert Schaller and the other, anonymous, reviewers for their contribution to the peer review of this work.

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Shimada, T.L., Shimada, T., Okazaki, Y. et al. HIGH STEROL ESTER 1 is a key factor in plant sterol homeostasis. Nat. Plants 5, 1154–1166 (2019). https://doi.org/10.1038/s41477-019-0537-2

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