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Title: The Mitochondrial Unfolded Protein Response Is Mediated Cell-Non-autonomously by Retromer-Dependent Wnt Signaling.

Authors: Zhang, Qian; Wu, Xueying; Chen, Peng; Liu, Limeng; Xin, Nan; Tian, Ye; Dillin, Andrew

Published In Cell, (2018 08 09)

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.

PubMed ID: 30057120 Exiting the NIEHS site

MeSH Terms: Animals; Animals, Genetically Modified/genetics; Animals, Genetically Modified/growth & development; Animals, Genetically Modified/metabolism*; Caenorhabditis elegans Proteins/genetics; Caenorhabditis elegans Proteins/metabolism*; Caenorhabditis elegans/genetics; Caenorhabditis elegans/growth & development; Caenorhabditis elegans/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*

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