Mitochondrial Membrane Potential-dependent Endoplasmic Reticulum Fragmentation is an Important Step in Neuritic Degeneration

被引：16

作者：

Bao, Fei-Xiang ^{[1
,2
]}

Shi, Hong-Yan ^{[1
,2
,3
]}

Long, Qi ^{[1
,2
]}

Yang, Liang ^{[1
,2
]}

Wu, Yi ^{[1
,2
]}

Ying, Zhong-Fu ^{[1
,2
]}

Qin, Da-Jiang ^{[1
,2
]}

Zhang, Jian ^{[1
,2
]}

Guo, Yi-Ping ^{[1
,2
]}

Li, Hong-Mei ^{[1
,2
]}

Liu, Xing-Guo ^{[1
,2
]}

机构：

[1] Univ Sci & Technol China, Hefei, Anhui, Peoples R China

[2] Chinese Acad Sci, Guangzhou Inst Biomed & Hlth, South China Inst Stem Cell Biol & Regenerat Med, Key Lab Regenerat Biol,Guangdong Prov Key Lab Ste, Guangzhou, Guangdong, Peoples R China

[3] Anhui Univ, Inst Hlth Sci, Hefei, Peoples R China

来源：

CNS NEUROSCIENCE & THERAPEUTICS | 2016年 / 22卷 / 08期

关键词：

MARIE-TOOTH-DISEASE; PERMEABILITY TRANSITION PORE; AXONAL-TRANSPORT; DENDRITIC SPINES; OXIDATIVE STRESS; MOTOR-NEURONS; ER; CELLS; DYSFUNCTION; LEADS;

D O I：

10.1111/cns.12547

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Background: Neuritic degeneration is an important early pathological step in neurodegeneration. Aim: The purpose of this study was to explore the mechanisms connecting neuritic degeneration to the functional and morphological remodeling of endoplasmic reticulum (ER) and mitochondria. Methods: Here, we set up neuritic degeneration models by neurite cutting-induced neural degeneration in human-induced pluripotent stem cell-derived neurons. Results: We found that neuritic ER becomes fragmented and forms complexes with mitochondria, which induces IP3R-dependent mitochondrial Ca2+ elevation and dysfunction during neuritic degeneration. Furthermore, mitochondrial membrane potential is required for ER fragmentation and mitochondrial Ca2+ elevation during neuritic degeneration. Mechanically, tightening of the ER-mitochondria associations by expression of a short "synthetic linker" and ER Ca2+ releasing together could promote mitochondrial Ca2+ elevation, dysfunction, and reactive oxygen species generation. Conclusion: Our study reveals a dynamic remodeling of the ER-mitochondria interface underlying neuritic degeneration.

引用

页码：648 / 660

页数：13

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