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 ofcco-1(complex IV subunit) in neurons ofC.elegansresults in the Wnt-dependent induction of cell-non-autonomous UPRmtin 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 UPRmtin a retromer complex-, Wnt signaling-, and serotonin-dependent manner, clearly implicating Wnt signaling as a strong candidate for the “mitokine” signal.
| 论文编号: | DOI:10.1016/j.cell.2018.06.029 |
| 论文题目: | The Mitochondrial Unfolded Protein Response Is Mediated Cell-Non-autonomously by Retromer-Dependent Wnt Signaling |
| 英文论文题目: | The Mitochondrial Unfolded Protein Response Is Mediated Cell-Non-autonomously by Retromer-Dependent Wnt Signaling |
| 第一作者: | Qian Zhang, Xueying Wu, Peng Chen, Limeng Liu, Nan Xin, Ye Tian, Andrew Dillin |
| 英文第一作者: | Qian Zhang, Xueying Wu, Peng Chen, Limeng Liu, Nan Xin, Ye Tian, Andrew Dillin |
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| 发表年度: | 2018-07-27 |
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| 摘要: | 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 ofcco-1(complex IV subunit) in neurons ofC.elegansresults in the Wnt-dependent induction of cell-non-autonomous UPRmtin 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 UPRmtin a retromer complex-, Wnt signaling-, and serotonin-dependent manner, clearly implicating Wnt signaling as a strong candidate for the “mitokine” signal. |
| 英文摘要: | 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 ofcco-1(complex IV subunit) in neurons ofC.elegansresults in the Wnt-dependent induction of cell-non-autonomous UPRmtin 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 UPRmtin a retromer complex-, Wnt signaling-, and serotonin-dependent manner, clearly implicating Wnt signaling as a strong candidate for the “mitokine” signal. |
| 刊物名称: | Cell |
| 英文刊物名称: | Cell |
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| 其它备注: | Qian Zhang, Xueying Wu, Peng Chen, Limeng Liu, Nan Xin, Ye Tian, Andrew Dillin. The Mitochondrial Unfolded Protein Response Is Mediated Cell-Non-autonomously by Retromer-Dependent Wnt Signaling. Cell. DOI:10.1016/j.cell.2018.06.029 |
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