The Mitochondrial Unfolded Protein Response Is Mediated Cell-Non-autonomously by Retromer-Dependent Wnt Signaling.
The Mitochondrial Unfolded Protein Response Is Mediated Cell-Non-autonomously by Retromer-Dependent Wnt Signaling.
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DOI：
10.1016/j.cell.2018.06.029
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发表时间：
2018-08-09
期刊：
影响因子：
64.5
通讯作者：
Dillin A
中科院分区：
文献类型：
--
作者：
Zhang Q;Wu X;Chen P;Liu L;Xin N;Tian Y;Dillin A
线粒体未折叠蛋白反应（UPRmt）可以在多个组织中以细胞非自主方式触发，以响应线粒体功能障碍。交流有关线粒体应激存在的信息的能力使全球反应能够最终更好地保护生物体免受局部线粒体挑战。我们发现，动物使用逆转录酶依赖的Wnt信号传播线粒体应激信号从神经系统到外周组织。具体而言，polyQ 40触发的线粒体应激激活或cco-1（复合物IV亚基）在C. elegans导致外周细胞中细胞非自主UPRmt的Wnt依赖性诱导。负责回收Wnt分泌因子/β-14的逆转录复合物组分的功能丧失突变阻止Wnt分泌，从而抑制细胞非自主UPRmt。Wnt配体/EGL-20的神经元表达足以以逆转录聚合物复合物、Wnt信号传导和降钙素依赖性方式诱导细胞非自主UPRmt，清楚地暗示Wnt信号传导是“丝裂因子”信号的强候选者。Wnt/EGL-20将线粒体应激信号从神经元传递到外周组织。
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 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. The Wnt/EGL-20 relays mitochondrial stress signals from neurons to peripheral tissues.
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影响因子：
11.8
作者：
Haynes, Cole M.;Petrova, Kseniya;Ron, David
通讯作者：
Ron, David
影响因子：
64.5
作者：
Durieux J;Wolff S;Dillin A
通讯作者：
Dillin A
影响因子：
11.8
作者：
Higuchi-Sanabria R;Frankino PA;Paul JW 3rd;Tronnes SU;Dillin A
通讯作者：
Dillin A
DOI：
10.1073/pnas.1319947111
发表时间：
2014-02-18
影响因子：
11.1
作者：
Gleason, Ryan J.;Akintobi, Adenrele M.;Padgett, Richard W.
通讯作者：
Padgett, Richard W.
影响因子：
56.9
作者：
Dillin, A;Hsu, AL;Kenyon, C
通讯作者：
Kenyon, C