title: Mitochondrial Membrane Potential-dependent Endoplasmic Reticulum Fragmentation is an Important Step in Neuritic Degeneration.
abstract: Neuritic degeneration is an important early pathological step in neurodegeneration.
  
  
  
  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.
  
  
  
  Here, we set up neuritic degeneration models by neurite cutting-induced neural degeneration in human-induced pluripotent stem cell-derived neurons.
  
  
  
  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.
  
  
  
  Our study reveals a dynamic remodeling of the ER-mitochondria interface underlying neuritic degeneration.
authors.affiliation: University of Science and Technology of China, Hefei, Anhui, China.|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.
authors.forename: Fei-Xiang
authors.initials: FX
authors.lastname: Bao
authors.affiliation: University of Science and Technology of China, Hefei, Anhui, China.|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.|Institute of Health Sciences, Anhui University, Hefei, China.
authors.forename: Hong-Yan
authors.initials: HY
authors.lastname: Shi
authors.affiliation: University of Science and Technology of China, Hefei, Anhui, China.|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.
authors.forename: Qi
authors.initials: Q
authors.lastname: Long
authors.affiliation: University of Science and Technology of China, Hefei, Anhui, China.|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.
authors.forename: Liang
authors.initials: L
authors.lastname: Yang
authors.affiliation: University of Science and Technology of China, Hefei, Anhui, China.|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.
authors.forename: Yi
authors.initials: Y
authors.lastname: Wu
authors.affiliation: University of Science and Technology of China, Hefei, Anhui, China.|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.
authors.forename: Zhong-Fu
authors.initials: ZF
authors.lastname: Ying
authors.affiliation: University of Science and Technology of China, Hefei, Anhui, China.|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.
authors.forename: Da-Jiang
authors.initials: DJ
authors.lastname: Qin
authors.affiliation: University of Science and Technology of China, Hefei, Anhui, China.|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.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
authors.affiliation: University of Science and Technology of China, Hefei, Anhui, China.|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.
authors.forename: Yi-Ping
authors.initials: YP
authors.lastname: Guo
authors.affiliation: University of Science and Technology of China, Hefei, Anhui, China.|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.
authors.forename: Hong-Mei
authors.initials: HM
authors.lastname: Li
authors.affiliation: University of Science and Technology of China, Hefei, Anhui, China.|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.
authors.forename: Xing-Guo
authors.initials: XG
authors.lastname: Liu
mesh_terms: D017209:Apoptosis; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D004721:Endoplasmic Reticulum / Q000502:physiology*; D005333:Fetus; D057809:HEK293 Cells; D006801:Humans; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial / Q000502:physiology*; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D009410:Nerve Degeneration / Q000503:physiopathology*; D016501:Neurites / Q000502:physiology / Q000648:ultrastructure*; D009474:Neurons / Q000187:drug effects / Q000648:ultrastructure*; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology; D039904:Pluripotent Stem Cells / Q000187:drug effects; D061209:Proton Ionophores / Q000494:pharmacology; D017382:Reactive Oxygen Species
chemical_list: D008164:Luminescent Proteins; D009838:Oligodeoxyribonucleotides; D061209:Proton Ionophores; D017382:Reactive Oxygen Species; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone
keywords: Ca2+; Endoplasmic reticulum-mitochondria coupling; Mitochondrial membrane potential; Neuron degeneration