A sphingolipid-mTORC1 nutrient-sensing pathway regulates animal development by an intestinal peroxisome relocation-based gut-brain crosstalk

Na Li; Beilei Hua; Qing Chen; Fukang Teng; Meiyu Ruan; Mengnan Zhu; Li Zhang; Yinbo Huo; Hongqin Liu; Min Zhuang; Huali Shen; Huanhu Zhu

Cell Reports (Jul 2022)

A sphingolipid-mTORC1 nutrient-sensing pathway regulates animal development by an intestinal peroxisome relocation-based gut-brain crosstalk

Na Li,
Beilei Hua,
Qing Chen,
Fukang Teng,
Meiyu Ruan,
Mengnan Zhu,
Li Zhang,
Yinbo Huo,
Hongqin Liu,
Min Zhuang,
Huali Shen,
Huanhu Zhu

Affiliations

Na Li: School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China; CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai 201210, China; University of Chinese Academy of Sciences, Beijing 100000, China
Beilei Hua: School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China
Qing Chen: School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China
Fukang Teng: School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China
Meiyu Ruan: School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China
Mengnan Zhu: School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China; CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai 201210, China; University of Chinese Academy of Sciences, Beijing 100000, China
Li Zhang: School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China
Yinbo Huo: School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China; CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai 201210, China; University of Chinese Academy of Sciences, Beijing 100000, China
Hongqin Liu: School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China
Min Zhuang: School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China
Huali Shen: Institutes of Biomedical Sciences, Department of Systems Biology for Medicine and School of Basic Medical Sciences, Fudan University, Shanghai 200032, China
Huanhu Zhu: School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China; Corresponding author

Journal volume & issue: Vol. 40, no. 4
p. 111140

Abstract

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Summary: The mTOR-dependent nutrient-sensing and response machinery is the central hub for animals to regulate their cellular and developmental programs. However, equivalently pivotal nutrient and metabolite signals upstream of mTOR and developmental-regulatory signals downstream of mTOR are not clear, especially at the organism level. We previously showed glucosylceramide (GlcCer) acts as a critical nutrient and metabolite signal for overall amino acid levels to promote development by activating the intestinal mTORC1 signaling pathway. Here, through a large-scale genetic screen, we find that the intestinal peroxisome is critical for antagonizing the GlcCer-mTORC1-mediated nutrient signal. Mechanistically, GlcCer deficiency, inactive mTORC1, or prolonged starvation relocates intestinal peroxisomes closer to the apical region in a kinesin- and microtubule-dependent manner. Those apical accumulated peroxisomes further release peroxisomal-β-oxidation-derived glycolipid hormones that target chemosensory neurons and downstream nuclear hormone receptor DAF-12 to arrest the animal development. Our data illustrate a sophisticated gut-brain axis that predominantly orchestrates nutrient-sensing-dependent development in animals.

CP: Cell biology

Published in Cell Reports

ISSN: 2211-1247 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Biology (General)
Website: http://www.cell.com/cell-reports/home

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