Endoplasmic reticulum mediates mitochondrial transfer within the osteocyte dendritic network
Endoplasmic reticulum mediates mitochondrial transfer within the osteocyte dendritic network
复制标题
内质网介导骨细胞树突网络内的线粒体转移
DOI：
10.1126/sciadv.aaw7215
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发表时间：
2019-11-01
期刊：
影响因子：
13.6
通讯作者：
Zheng, Ming H.
中科院分区：
文献类型：
--
作者：
Gao, Junjie;Qin, An;Zheng, Ming H.
内质网介导的细胞间线粒体转移对组织稳态至关重要。线粒体转移在组织稳态调节和肿瘤化疗抵抗中起着至关重要的作用。骨细胞具有相互连接的树突网络，是研究其机制的一个模型。我们已经证明，在具有光激活线粒体（PhAM）的原代小鼠骨细胞和MLO-Y4细胞中，通过高分辨率共聚焦成像可以看到树突网络中的线粒体转移。正常骨细胞将线粒体转移到邻近的代谢应激骨细胞，恢复其代谢功能。树突网络内线粒体的协调运动和转移依赖于内质网和线粒体之间的接触。Mitofusin 2 (Mfn2)，一种将内质网连接到线粒体的GTPase，主要介导这种转移。随着年龄的增长，Mfn2表达的下降伴随着骨细胞树突状网络中线粒体分布和转移的受损。这些数据显示了er -线粒体接触在介导线粒体转移中的先前未知的功能，并提供了解释骨细胞稳态的机制。
Intercellular mitochondrial transfer mediated by the endoplasmic reticulum is essential for tissue homeostasis. Mitochondrial transfer plays a crucial role in the regulation of tissue homeostasis and resistance to cancer chemotherapy. Osteocytes have interconnecting dendritic networks and are a model to investigate its mechanism. We have demonstrated, in primary murine osteocytes with photoactivatable mitochondria (PhAM)floxed and in MLO-Y4 cells, mitochondrial transfer in the dendritic networks visualized by high-resolution confocal imaging. Normal osteocytes transferred mitochondria to adjacent metabolically stressed osteocytes and restored their metabolic function. The coordinated movement and transfer of mitochondria within the dendritic network rely on contact between the endoplasmic reticulum (ER) and mitochondria. Mitofusin 2 (Mfn2), a GTPase that tethers ER to mitochondria, predominantly mediates the transfer. A decline in Mfn2 expression with age occurs concomitantly with both impaired mitochondrial distribution and transfer in the osteocyte dendritic network. These data show a previously unknown function of ER-mitochondrial contact in mediating mitochondrial transfer and provide a mechanism to explain the homeostasis of osteocytes.