| RRC ID |
56246
|
| 著者 |
Zhang Q, Wu X, Chen P, Liu L, Xin N, Tian Y, Dillin A.
|
| タイトル |
The Mitochondrial Unfolded Protein Response Is Mediated Cell-Non-autonomously by Retromer-Dependent Wnt Signaling.
|
| ジャーナル |
Cell
|
| Abstract |
The mitochondrial unfolded protein response (UPRmt) can be triggered in a cell-non-autonomous fashion across multiple tissues in response to mitochondrial dysfunction. The ability to communicate information about the presence of mitochondrial stress enables a global response that can ultimately better protect an organism from local mitochondrial challenges. We find that animals use retromer-dependent Wnt signaling to propagate mitochondrial stress signals from the nervous system to peripheral tissues. Specifically, the polyQ40-triggered activation of mitochondrial stress or reduction of cco-1 (complex IV subunit) in neurons of C. elegans results in the Wnt-dependent induction of cell-non-autonomous UPRmt in peripheral cells. Loss-of-function mutations of retromer complex components that are responsible for recycling the Wnt secretion-factor/MIG-14 prevent Wnt secretion and thereby suppress cell-non-autonomous UPRmt. Neuronal expression of the Wnt ligand/EGL-20 is sufficient to induce cell-non-autonomous UPRmt in a retromer complex-, Wnt signaling-, and serotonin-dependent manner, clearly implicating Wnt signaling as a strong candidate for the "mitokine" signal.
|
| 巻・号 |
174(4)
|
| ページ |
870-883.e17
|
| 公開日 |
2018-8-9
|
| DOI |
10.1016/j.cell.2018.06.029
|
| PII |
S0092-8674(18)30797-9
|
| PMID |
30057120
|
| PMC |
PMC6086732
|
| MeSH |
Animals
Animals, Genetically Modified / genetics
Animals, Genetically Modified / growth & development
Animals, Genetically Modified / metabolism*
Caenorhabditis elegans / genetics
Caenorhabditis elegans / growth & development
Caenorhabditis elegans / metabolism*
Caenorhabditis elegans Proteins / genetics
Caenorhabditis elegans Proteins / metabolism*
Carrier Proteins / genetics
Carrier Proteins / metabolism
Glycoproteins / genetics
Glycoproteins / metabolism
Intracellular Signaling Peptides and Proteins
Mitochondria / genetics
Mitochondria / metabolism*
Neurons / cytology
Neurons / metabolism
Polyubiquitin / metabolism*
Unfolded Protein Response / physiology*
Vesicular Transport Proteins / genetics
Vesicular Transport Proteins / metabolism
Wnt Proteins / genetics
Wnt Proteins / metabolism*
|
| IF |
36.216
|
| 引用数 |
37
|
| リソース情報 |
| 線虫 |
tm1523
tm1320
tm1108
tm1325 |
