Ad4BP/SF-1 regulates cholesterol synthesis to boost the production of steroids

Baba Takashi

Otake Hiroyuki

Inoue Miki

Sato Tetsuya

Ishihara Yasuhiro

Moon Ju-Yeon

Tsuchiya Megumi

Miyabayashi Kanako

Ogawa Hidesato

Shima Yuichi

Wang Lixiang

Sato Ryuichiro

Yamazaki Takeshi

Suyama Mikita

Nomura Masatoshi

Choi Man Ho

Ohkawa Yasuyuki

Morohashi Ken-ichirou

Communications Biology

Housekeeping metabolic pathways such as glycolysis are active in all cell types. In addition, many types of cells are equipped with cell-specific metabolic pathways. To properly perform their functions, housekeeping and cell-specific metabolic pathways must function cooperatively. However, the regulatory mechanisms that couple metabolic pathways remain largely unknown. Recently, we showed that the steroidogenic cell-specific nuclear receptor Ad4BP/ SF-1, which regulates steroidogenic genes, also regulates housekeeping glycolytic genes. Here, we identify cholesterogenic genes as the targets of Ad4BP/SF-1. Further, we reveal that Ad4BP/SF-1 regulates Hummr, a candidate mediator of cholesterol transport from endoplasmic reticula to mitochondria. Given that cholesterol is the starting material for steroidogenesis and is synthesized from acetyl-CoA, which partly originates from glucose, our results suggest that multiple biological processes involved in synthesizing steroid hormones are governed by Ad4BP/SF-1. To our knowledge, this study provides the first example where housekeeping and cell-specific metabolism are coordinated at the transcriptional level.

eng

Nature Research

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[ISSN] 2399-3642

[DOI] 10.1038/s42003-018-0020-z

[PMID] 30271905

[DOI] https://doi.org/10.1038/s42003-018-0020-z