RRC ID 56246
Author Zhang Q, Wu X, Chen P, Liu L, Xin N, Tian Y, Dillin A.
Title The Mitochondrial Unfolded Protein Response Is Mediated Cell-Non-autonomously by Retromer-Dependent Wnt Signaling.
Journal 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.
Volume 174(4)
Pages 870-883.e17
Published 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
Times Cited 37
Altmetric score
オルトメトリクス指標項目
The most frequently cited source X(Twitter)
Total number of mentions 153
Altmetric score changes over past 6months 0.0
Resource
C.elegans tm1523 tm1320 tm1108 tm1325