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.
Keywords: C.elegans; CP: Cell biology; ascaroside; diapause; glucosylceramide; gut-brain axis; hormone; mTOR pathway; metabolism; nutrient sensing; peroxisome repositioning.
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