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

• Qian Zhang ^[1] ; Xueying Wu ^[1] ; Peng Chen ^[1]
  1. [1] Chinese Academy of Sciences

     Chinese Academy of Sciences

     China

     
• Localización: Cell, ISSN 0092-8674, Vol. 174, Nº. 4, 2018, págs. 870-883
• Idioma: inglés
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• Resumen

  • The mitochondrial unfolded protein response (UPR mt) 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 UPR mt 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 UPR mt. Neuronal expression of the Wnt ligand/EGL-20 is sufficient to induce cell-non-autonomous UPR mt in a retromer complex-, Wnt signaling-, and serotonin-dependent manner, clearly implicating Wnt signaling as a strong candidate for the “mitokine” signal.