Endoplasmic reticulum mediates mitochondrial transfer within the osteocyte dendritic network

Junjie Gao, An Qin, Delin Liu, Rui Ruan, Qiyang Wang, Jun Yuan, Tak Sum Cheng, Aleksandra Filipovska, J. M. Papadimitriou, Kerong Dai, Qing Jiang, Xiang Gao, Jian Q. Feng, Hiroshi Takayanagi, Changqing Zhang, Ming H. Zheng

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Article numbereaaw7215
JournalScience Advances
Volume5
Issue number11
DOIs
Publication statusPublished - 20 Nov 2019

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endoplasmic reticulum
mitochondria
homeostasis
chemotherapy
cancer
high resolution
cells

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Gao, Junjie ; Qin, An ; Liu, Delin ; Ruan, Rui ; Wang, Qiyang ; Yuan, Jun ; Cheng, Tak Sum ; Filipovska, Aleksandra ; Papadimitriou, J. M. ; Dai, Kerong ; Jiang, Qing ; Gao, Xiang ; Feng, Jian Q. ; Takayanagi, Hiroshi ; Zhang, Changqing ; Zheng, Ming H. / Endoplasmic reticulum mediates mitochondrial transfer within the osteocyte dendritic network. In: Science Advances. 2019 ; Vol. 5, No. 11.
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abstract = "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.",
author = "Junjie Gao and An Qin and Delin Liu and Rui Ruan and Qiyang Wang and Jun Yuan and Cheng, {Tak Sum} and Aleksandra Filipovska and Papadimitriou, {J. M.} and Kerong Dai and Qing Jiang and Xiang Gao and Feng, {Jian Q.} and Hiroshi Takayanagi and Changqing Zhang and Zheng, {Ming H.}",
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Gao, J, Qin, A, Liu, D, Ruan, R, Wang, Q, Yuan, J, Cheng, TS, Filipovska, A, Papadimitriou, JM, Dai, K, Jiang, Q, Gao, X, Feng, JQ, Takayanagi, H, Zhang, C & Zheng, MH 2019, 'Endoplasmic reticulum mediates mitochondrial transfer within the osteocyte dendritic network' Science Advances, vol. 5, no. 11, eaaw7215. https://doi.org/10.1126/sciadv.aaw7215

Endoplasmic reticulum mediates mitochondrial transfer within the osteocyte dendritic network. / Gao, Junjie; Qin, An; Liu, Delin; Ruan, Rui; Wang, Qiyang; Yuan, Jun; Cheng, Tak Sum; Filipovska, Aleksandra; Papadimitriou, J. M.; Dai, Kerong; Jiang, Qing; Gao, Xiang; Feng, Jian Q.; Takayanagi, Hiroshi; Zhang, Changqing; Zheng, Ming H.

In: Science Advances, Vol. 5, No. 11, eaaw7215, 20.11.2019.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Endoplasmic reticulum mediates mitochondrial transfer within the osteocyte dendritic network

AU - Gao, Junjie

AU - Qin, An

AU - Liu, Delin

AU - Ruan, Rui

AU - Wang, Qiyang

AU - Yuan, Jun

AU - Cheng, Tak Sum

AU - Filipovska, Aleksandra

AU - Papadimitriou, J. M.

AU - Dai, Kerong

AU - Jiang, Qing

AU - Gao, Xiang

AU - Feng, Jian Q.

AU - Takayanagi, Hiroshi

AU - Zhang, Changqing

AU - Zheng, Ming H.

PY - 2019/11/20

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AB - 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.

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