| RRC ID |
76221
|
| Author |
Li N, Hua B, Chen Q, Teng F, Ruan M, Zhu M, Zhang L, Huo Y, Liu H, Zhuang M, Shen H, Zhu H.
|
| Title |
A sphingolipid-mTORC1 nutrient-sensing pathway regulates animal development by an intestinal peroxisome relocation-based gut-brain crosstalk.
|
| Journal |
Cell Rep
|
| Abstract |
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.
|
| Volume |
40(4)
|
| Pages |
111140
|
| Published |
2022-7-26
|
| DOI |
10.1016/j.celrep.2022.111140
|
| PII |
S2211-1247(22)00949-4
|
| PMID |
35905721
|
| MeSH |
Animals
Brain / metabolism
Mechanistic Target of Rapamycin Complex 1 / metabolism
Nutrients
Peroxisomes* / metabolism
Sphingolipids* / metabolism
TOR Serine-Threonine Kinases / metabolism
|
| Resource |
| C.elegans |
tm1027
tm1192
tm504
tm1964
tm6454
tm6502
tm11887
tm4948 |
