期刊
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
卷 605, 期 -, 页码 63-69出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2022.03.061
关键词
Sphingolipid; Long-chain base; Dihydrosphingosine; Saccharomyces cerevisiae; Signal transduction
资金
- KAKENHI from the Ministry of Education, Culture, Sports, Science, and Technology, Japan [21H02118]
- Noda Institute for Scientific Research, Japan
- Ohsumi Frontier Science Fundation, Japan
The cytotoxicity of dihydrosphingosine (DHS) is partially mediated through activation of the RTG pathway.
Sphingoid long-chain bases are essential intermediates of ceramides and complex sphingolipids, and function in the regulation of various signal transduction systems. Previously, we found that, in budding yeast, intracellularly accumulated dihydrosphingosine (DHS) causes mitochondrial reactive-oxygen species (ROS)-mediated cytotoxicity, which is much stronger than phytosphingosine. In this study, we screened for suppressor mutations that confer resistance to DHS, and identified RTG2, which encodes upregulation of the mitochondrial retrograde signaling pathway (RTG pathway). Deletion of RTG3 encoding transcriptional factor for the RTG pathway suppressed the cytotoxicity of DHS, whereas deletion of MKS1 or point mutation of LST8, both of which cause increased activity of the RTG pathway, enhanced the cytotoxicity. Moreover, the deletion of RTG3 also suppressed the DHS-induced increases in ROS levels. Finally, it was found that the RTG pathway is activated on DHS treatment. These results suggested that the cytotoxicity of DHS is partially mediated through activation of the RTG pathway. (C) 2022 Elsevier Inc. All rights reserved.
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