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The role of Mfn2 in the structure and function of endoplasmic reticulum-mitochondrial tethering in vivo.
Han, Song; Zhao, Fanpeng; Hsia, Jeffrey; Ma, Xiaopin; Liu, Yi; Torres, Sandy; Fujioka, Hisashi; Zhu, Xiongwei.
Afiliación
  • Han S; Department of Pathology, Case Western Reserve University, Cleveland, OH 44106, USA.
  • Zhao F; Department of Pathophysiology, School of Basic Medical Sciences, Wuhan University, Wuhan, Hubei 430072, China.
  • Hsia J; Department of Pathology, Case Western Reserve University, Cleveland, OH 44106, USA.
  • Ma X; Department of Pathology, Case Western Reserve University, Cleveland, OH 44106, USA.
  • Liu Y; Department of Pathology, Case Western Reserve University, Cleveland, OH 44106, USA.
  • Torres S; Department of Pathology, Case Western Reserve University, Cleveland, OH 44106, USA.
  • Fujioka H; Department of Pathology, Case Western Reserve University, Cleveland, OH 44106, USA.
  • Zhu X; Cryo-Electron Microscopy Core Facility, Case Western Reserve University, Cleveland, OH 44106, USA.
J Cell Sci ; 134(13)2021 07 01.
Article en En | MEDLINE | ID: mdl-34110411
Mitochondria-endoplasmic reticulum contacts (MERCs) play an essential role in multiple cell physiological processes. Although Mfn2 was the first protein implicated in the formation of MERCs, there is debate as to whether it acts as a tether or antagonizer, largely based on in vitro studies. To understand the role of Mfn2 in MERCs in vivo, we characterized ultrastructural and biochemical changes of MERCs in pyramidal neurons of hippocampus in Mfn2 conditional knockout mice and in Mfn2 overexpressing mice, and found that Mfn2 ablation caused reduced close contacts, whereas Mfn2 overexpression caused increased close contacts between the endoplasmic reticulum (ER) and mitochondria in vivo. Functional studies on SH-SY5Y cells with Mfn2 knockout or overexpression demonstrating similar biochemical changes found that mitochondrial calcium uptake along with IP3R3-Grp75 interaction was decreased in Mfn2 knockout cells but increased in Mfn2 overexpressing cells. Lastly, we found Mfn2 knockout decreased and Mfn2 overexpression increased the interaction between the ER-mitochondria tethering pair of VAPB-PTPIP51. In conclusion, our study supports the notion that Mfn2 plays a critical role in ER-mitochondrial tethering and the formation of close contacts in neuronal cells in vivo.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteínas Mitocondriales / Retículo Endoplásmico Límite: Animals Idioma: En Revista: J Cell Sci Año: 2021 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteínas Mitocondriales / Retículo Endoplásmico Límite: Animals Idioma: En Revista: J Cell Sci Año: 2021 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido