Lysosomal activity maintains glycolysis and cyclin E1 expression by mediating Ad4BP/SF-1 stability for proper steroidogenic cell growth.
The development and differentiation of steroidogenic organs are controlled by Ad4BP/SF-1 (adrenal 4 binding protein/steroidogenic factor 1). Besides, lysosomal activity is required for steroidogenesis and also enables adrenocortical cell to survive during stress. However, the role of lysosomal activity on steroidogenic cell growth is as yet unknown. Here, we showed that lysosomal activity maintained Ad4BP/SF-1 protein stability for proper steroidogenic cell growth. Treatment of cells with lysosomal inhibitors reduced steroidogenic cell growth in vitro. Suppression of autophagy did not affect cell growth indicating that autophagy was dispensable for steroidogenic cell growth. When lysosomal activity was inhibited, the protein stability of Ad4BP/SF-1 was reduced leading to reduced S phase entry. Interestingly, treatment of cells with lysosomal inhibitors reduced glycolytic gene expression and supplying the cells with pyruvate alleviated the growth defect. ChIP-sequence/ChIP studies indicated that Ad4BP/SF-1 binds to the upstream region of Ccne1 (cyclin E1) gene during G1/S phase. In addition, treatment of zebrafish embryo with lysosomal inhibitor reduced the levels of the interrenal (adrenal) gland markers. Thus lysosomal activity maintains steroidogenic cell growth via stabilizing Ad4BP/SF-1 protein.
Department of Cell Biology and Anatomy, College of Medicine, National Cheng Kung University, Tainan, 701, Taiwan.|Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, 701, Taiwan.
Jhih-Siang
JS
Syu
Division of Molecular Life Science, Graduate School of Systems Life Science, Kyushu University, Maidashi 3-1-1, Higashi-ku, Fukuoka, 812-8582, Japan.|Department of Molecular Biology, Graduate School of Medical Sciences, Kyushu University, Maidashi 3-1-1, Higashi-ku, Fukuoka, 812-8582, Japan.
Takashi
T
Baba
Division of Genetics, Department of Obstetrics and Gynecology, National Cheng Kung University Hospital, Tainan, 704, Taiwan.
Jyun-Yuan
JY
Huang
Advanced ICT Research Institute Kobe, National Institute of Information and Communications Technology, Iwaoka 588-2, Nishi-ku, Kobe, 651-2492, Japan.
Hidesato
H
Ogawa
Department of Biotechnology and Bioindustry Sciences, College of Bioscience and Biotechnology, National Cheng Kung University, Tainan, 701, Taiwan.|Institute of Biotechnology, College of Bioscience and Biotechnology, National Cheng Kung University, Tainan, 701, Taiwan.
Chi-Han
CH
Hsieh
Department of Biotechnology and Bioindustry Sciences, College of Bioscience and Biotechnology, National Cheng Kung University, Tainan, 701, Taiwan.|Institute of Biotechnology, College of Bioscience and Biotechnology, National Cheng Kung University, Tainan, 701, Taiwan.
Jin-Xian
JX
Hu
Department of Cell Biology and Anatomy, College of Medicine, National Cheng Kung University, Tainan, 701, Taiwan.|Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, 701, Taiwan.
Ting-Yu
TY
Chen
Department of Cell Biology and Anatomy, College of Medicine, National Cheng Kung University, Tainan, 701, Taiwan.
Tzu-Chien
TC
Lin
Graduate School of Frontier Biosciences, Osaka University, 1-3 Yamadaoka, Suita, 565-0871, Japan.
Megumi
M
Tsuchiya
Division of Molecular Life Science, Graduate School of Systems Life Science, Kyushu University, Maidashi 3-1-1, Higashi-ku, Fukuoka, 812-8582, Japan.|Department of Molecular Biology, Graduate School of Medical Sciences, Kyushu University, Maidashi 3-1-1, Higashi-ku, Fukuoka, 812-8582, Japan.
Ken-Ichirou
KI
Morohashi
Department of Cell Biology and Anatomy, College of Medicine, National Cheng Kung University, Tainan, 701, Taiwan. bumiin@mail.ncku.edu.tw.|Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, 404, Taiwan. bumiin@mail.ncku.edu.tw.
Bu-Miin
BM
Huang
Department of Biotechnology and Bioindustry Sciences, College of Bioscience and Biotechnology, National Cheng Kung University, Tainan, 701, Taiwan. fuilu@mail.ncku.edu.tw.|Institute of Biotechnology, College of Bioscience and Biotechnology, National Cheng Kung University, Tainan, 701, Taiwan. fuilu@mail.ncku.edu.tw.
Fu-L
FL
Lu
Department of Cell Biology and Anatomy, College of Medicine, National Cheng Kung University, Tainan, 701, Taiwan. b89609046@gmail.com.|Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, 701, Taiwan. b89609046@gmail.com.
Chia-Yih
CY
Wang
D000818:Animals; D049109:Cell Proliferation; D002478:Cells, Cultured; D019927:Cyclin E / Q000096:biosynthesis*; D006019:Glycolysis; D008247:Lysosomes / Q000378:metabolism*; D051379:Mice; D015513:Oncogene Proteins / Q000096:biosynthesis*; D054339:Steroidogenic Factor 1 / Q000378:metabolism*; D015027:Zebrafish / Q000196:embryology
D019927:Cyclin E; D015513:Oncogene Proteins; D054339:Steroidogenic Factor 1; C568314:cyclin E1, mouse