TY - JOUR
T1 - Involvement of the mitochondrial retrograde pathway in dihydrosphingosine-induced cytotoxicity in budding yeast
AU - Takayama, Chihiro
AU - Koga, Ayano
AU - Sakamoto, Risa
AU - Arita, Nobuaki
AU - Tani, Motohiro
N1 - Funding Information:
We wish to thank Drs. O. Kuge, T. Ogishima, and N. Miyata (Kyushu University) for the valuable suggestions regarding this study. This study was funded by KAKENHI ( 21H02118 ) from the Ministry of Education, Culture, Sports, Science, and Technology, Japan, the Noda Institute for Scientific Research , Japan, and the Ohsumi Frontier Science Fundation, Japan.
Funding Information:
We wish to thank Drs. O. Kuge, T. Ogishima, and N. Miyata (Kyushu University) for the valuable suggestions regarding this study. This study was funded by KAKENHI (21H02118) from the Ministry of Education, Culture, Sports, Science, and Technology, Japan, the Noda Institute for Scientific Research, Japan, and the Ohsumi Frontier Science Fundation, Japan.
Publisher Copyright:
© 2022 Elsevier Inc.
PY - 2022/5/21
Y1 - 2022/5/21
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85126521378&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85126521378&partnerID=8YFLogxK
U2 - 10.1016/j.bbrc.2022.03.061
DO - 10.1016/j.bbrc.2022.03.061
M3 - Article
C2 - 35316765
AN - SCOPUS:85126521378
VL - 605
SP - 63
EP - 69
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
SN - 0006-291X
ER -