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

Autor: Na Li, Beilei Hua, Qing Chen, Fukang Teng, Meiyu Ruan, Mengnan Zhu, Li Zhang, Yinbo Huo, Hongqin Liu, Min Zhuang, Huali Shen, Huanhu Zhu
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: Cell Reports, Vol 40, Iss 4, Pp 111140- (2022)
Druh dokumentu: article
ISSN: 2211-1247
DOI: 10.1016/j.celrep.2022.111140
Popis: 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.
Databáze: Directory of Open Access Journals