Fei-Xiang Bao1,2, Hong-Yan Shi1,2,3, Qi Long1,2, Liang Yang1,2, Yi Wu1,2, Zhong-Fu Ying1,2, Da-Jiang Qin1,2, Jian Zhang1,2, Yi-Ping Guo1,2, Hong-Mei Li1,2, Xing-Guo Liu1,2. 1. University of Science and Technology of China, Hefei, Anhui, China. 2. Key Laboratory of Regenerative Biology, Guangdong provincial Key Laboratory of Stem Cell and Regenerative Medicine, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China. 3. Institute of Health Sciences, Anhui University, Hefei, China.
Abstract
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 Ca(2+) elevation and dysfunction during neuritic degeneration. Furthermore, mitochondrial membrane potential is required for ER fragmentation and mitochondrial Ca(2+) elevation during neuritic degeneration. Mechanically, tightening of the ER-mitochondria associations by expression of a short "synthetic linker" and ER Ca(2+) releasing together could promote mitochondrial Ca(2+) elevation, dysfunction, and reactive oxygen species generation. CONCLUSION: Our study reveals a dynamic remodeling of the ER-mitochondria interface underlying neuritic degeneration.
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 Ca(2+) elevation and dysfunction during neuritic degeneration. Furthermore, mitochondrial membrane potential is required for ER fragmentation and mitochondrial Ca(2+) elevation during neuritic degeneration. Mechanically, tightening of the ER-mitochondria associations by expression of a short "synthetic linker" and ER Ca(2+) releasing together could promote mitochondrial Ca(2+) elevation, dysfunction, and reactive oxygen species generation. CONCLUSION: Our study reveals a dynamic remodeling of the ER-mitochondria interface underlying neuritic degeneration.
Authors: György Csordás; Christian Renken; Péter Várnai; Ludivine Walter; David Weaver; Karolyn F Buttle; Tamás Balla; Carmen A Mannella; György Hajnóczky Journal: J Cell Biol Date: 2006-09-18 Impact factor: 10.539
Authors: György Szabadkai; Katiuscia Bianchi; Péter Várnai; Diego De Stefani; Mariusz R Wieckowski; Dario Cavagna; Anikó I Nagy; Tamás Balla; Rosario Rizzuto Journal: J Cell Biol Date: 2006-12-18 Impact factor: 10.539
Authors: Janet Brownlees; Steven Ackerley; Andrew J Grierson; Nick J O Jacobsen; Kerry Shea; Brian H Anderton; P Nigel Leigh; Christopher E Shaw; Christopher C J Miller Journal: Hum Mol Genet Date: 2002-11-01 Impact factor: 6.150