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
C.elegans tm1523 tm1320 tm1108 tm1325