| RRC ID |
76222
|
| Author |
Li X, Li J, Zhu D, Zhang N, Hao X, Zhang W, Zhang Q, Liu Y, Wu X, Tian Y.
|
| Title |
Protein disulfide isomerase PDI-6 regulates Wnt secretion to coordinate inter-tissue UPRmt activation and lifespan extension in C. elegans.
|
| Journal |
Cell Rep
|
| Abstract |
Coordination of inter-tissue stress signaling is essential for organismal fitness. Neuronal mitochondrial perturbations activate the mitochondrial unfolded-protein response (UPRmt) in the intestine via the mitokine Wnt signaling in Caenorhabditis elegans. Here, we found that the protein disulfide isomerase PDI-6 coordinates inter-tissue UPRmt signaling via regulating the Wnt ligand EGL-20. PDI-6 is expressed in the endoplasmic reticulum (ER) and interacts with EGL-20 through disulfide bonds that are essential for EGL-20 stability and secretion. pdi-6 deficiency results in misfolded EGL-20, which leads to its degradation via ER-associated protein degradation (ERAD) machinery. Expression of PDI-6 declines drastically with aging, and animals with pdi-6 deficiency have decreased lifespan. Overexpression of PDI-6 is sufficient to maintain Wnt/EGL-20 protein levels during aging, activating the UPRmt, and significantly extending lifespan in a Wnt- and UPRmt-dependent manner. Our study reveals that protein disulfide isomerase facilitates Wnt secretion to coordinate the inter-tissue UPRmt signaling and organismal aging.
|
| Volume |
39(10)
|
| Pages |
110931
|
| Published |
2022-6-7
|
| DOI |
10.1016/j.celrep.2022.110931
|
| PII |
S2211-1247(22)00713-6
|
| PMID |
35675782
|
| MeSH |
Animals
Caenorhabditis elegans* / metabolism
Caenorhabditis elegans Proteins* / genetics
Caenorhabditis elegans Proteins* / metabolism
Longevity
Protein Disulfide-Isomerases / genetics
Protein Disulfide-Isomerases / metabolism
Unfolded Protein Response
Wnt Proteins / metabolism
|
| Resource |
| C.elegans |
tm2482 |
