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Peer-reviewedCC BY-NC-SA 4.0Molecular Biology of the Cell

HOG pathway-dependent protection against impaired complex sphingolipid biosynthesis involves Fmp48-mediated suppression of mitochondria-dependent ROS accumulation

  • Takatoshi Sudo1
  • Risa Sakamoto2
  • Kensei Yamanaka1
  • Saki Sugihara3
  • Motohiro Tani1,2,3
  1. 1Faculty of Applied Biological Sciences, Gifu University, 1-1 Yanagido, Gifu 501-1193, Japan
  2. 2Department of Chemistry, Faculty of Sciences, Kyushu University, 744, Motooka, Nishi-ku, Fukuoka 819-0395, Japan
  3. 3The United Graduate School of Agricultural Science, Gifu University, Yanagido 1-1, Gifu 501-1193, Japan
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Abstract

Complex sphingolipids are required for normal growth of the budding yeast Saccharomyces cerevisiae. Repression of AUR1, which encodes inositol phosphorylceramide synthase, disrupts sphingolipid homeostasis by reducing complex sphingolipid levels and promoting ceramide accumulation, ultimately causing growth inhibition and cell death. We previously showed that the high-osmolarity glycerol (HOG) pathway is activated under AUR1-repressive conditions and alleviates the resulting growth defect. In this study, among genes induced in a HOG pathway-dependent manner, we identified FMP48, UIP4, and MGA1, whose overexpression suppressed cell death caused by AUR1 repression. Simultaneous deletion of these genes had modest effects under AUR1 repression alone but more clearly impaired cytoprotection when HOG pathway signaling was enhanced. Neither deletion nor overexpression of these genes restored complex sphingolipid levels or prevented ceramide accumulation. AUR1 repression promoted mitochondria-dependent ROS accumulation, and the associated cell death was markedly reduced when mitochondrial electron transport was impaired. Loss of HOG1 further enhanced ROS accumulation. FMP48 overexpression suppressed ROS accumulation and cell death under AUR1-repressive conditions but did not further reduce cell death when mitochondrial electron transport was impaired. Together, these findings identify FMP48, UIP4, and MGA1 as contributors to HOG-dependent cytoprotection.

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Cite

BibTeXRIS
BibTeX
@article{sudo2026pathwaydependent,
  title = {{HOG pathway-dependent protection against impaired complex sphingolipid biosynthesis involves Fmp48-mediated suppression of mitochondria-dependent ROS accumulation}},
  author = {Takatoshi Sudo and Risa Sakamoto and Kensei Yamanaka and Saki Sugihara and Motohiro Tani},
  journal = {Molecular Biology of the Cell},
  year = {2026},
  month = oct,
  doi = {10.1091/mbc.e26-07-0335},
  url = {https://doi.org/10.1091/mbc.e26-07-0335},
  note = {CC BY-NC-SA 4.0},
}
RIS
TY  - JOUR
TI  - HOG pathway-dependent protection against impaired complex sphingolipid biosynthesis involves Fmp48-mediated suppression of mitochondria-dependent ROS accumulation
AU  - Takatoshi Sudo
AU  - Risa Sakamoto
AU  - Kensei Yamanaka
AU  - Saki Sugihara
AU  - Motohiro Tani
PY  - 2026
DA  - 2026/10/26
JO  - Molecular Biology of the Cell
DO  - 10.1091/mbc.e26-07-0335
UR  - https://doi.org/10.1091/mbc.e26-07-0335
AB  - Complex sphingolipids are required for normal growth of the budding yeast Saccharomyces cerevisiae. Repression of AUR1, which encodes inositol phosphorylceramide synthase, disrupts sphingolipid homeostasis by reducing complex sphingolipid levels and promoting ceramide accumulation, ultimately causing growth inhibition and cell death. We previously showed that the high-osmolarity glycerol (HOG) pathway is activated under AUR1-repressive conditions and alleviates the resulting growth defect. In this study, among genes induced in a HOG pathway-dependent manner, we identified FMP48, UIP4, and MGA1, whose overexpression suppressed cell death caused by AUR1 repression. Simultaneous deletion of these genes had modest effects under AUR1 repression alone but more clearly impaired cytoprotection when HOG pathway signaling was enhanced. Neither deletion nor overexpression of these genes restored complex sphingolipid levels or prevented ceramide accumulation. AUR1 repression promoted mitochondria-dependent ROS accumulation, and the associated cell death was markedly reduced when mitochondrial electron transport was impaired. Loss of HOG1 further enhanced ROS accumulation. FMP48 overexpression suppressed ROS accumulation and cell death under AUR1-repressive conditions but did not further reduce cell death when mitochondrial electron transport was impaired. Together, these findings identify FMP48, UIP4, and MGA1 as contributors to HOG-dependent cytoprotection.
SN  - 1059-1524
SN  - 1939-4586
ER  -