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Abstract
In eukaryotic cells, different organelles interact at membrane contact sites stabilized by tethers. Mitochondrial mitofusin 2 (MFN2) acts as a membrane tether that interacts with an unknown partner on the endoplasmic reticulum (ER). In this work, we identified the MFN2 splice variant ERMIT2 as the ER tethering partner of MFN2. Splicing of MFN2 produced ERMIT2 and ERMIN2, two ER-specific variants. ERMIN2 regulated ER morphology, whereas ERMIT2 localized at the ER-mitochondria interface and interacted with mitochondrial mitofusins to tether ER and mitochondria. This tethering allowed efficient mitochondrial calcium ion uptake and phospholipid transfer. Expression of ERMIT2 ameliorated the ER stress, inflammation, and fibrosis typical of liver-specific Mfn2 knockout mice. Thus, ER-specific MFN2 variants display entirely extramitochondrial MFN2 functions involved in interorganellar tethering and liver metabolic activities.
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Authors (19)
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Déborah Naón
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María Isabel Hernández-Alvarez
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Satoko Shinjo
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Saska Ivanova
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Olga Martins de Brito
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Albert Quintana
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Juan Hidalgo
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Manuel Palacín
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Pilar Aparicio
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Juan Castellanos
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Luis Lores
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David Sebastián
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Sonia Fernández-Veledo
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Joan Vendrell
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Jorge Joven
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Modesto Orozco
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Antonio Zorzano
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Luca Scorrano
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Keywords
Details
- Category:
- Articles
- Type:
- artykuły w czasopismach
- Published in:
-
SCIENCE
no. 380,
pages 1 - 13,
ISSN: 0036-8075 - Language:
- English
- Publication year:
- 2023
- Bibliographic description:
- Naón D., Hernández-Alvarez M. I., Shinjo S., Wieczór M., Ivanova S., Martins de Brito O., Quintana A., Hidalgo J., Palacín M., Aparicio P., Castellanos J., Lores L., Sebastián D., Fernández-Veledo S., Vendrell J., Joven J., Orozco M., Zorzano A., Scorrano L.: Splice variants of mitofusin 2 shape the endoplasmic reticulum and tether it to mitochondria// SCIENCE -Vol. 380,iss. 6651 (2023), s.1-13
- DOI:
- Digital Object Identifier (open in new tab) 10.1126/science.adh9351
- Sources of funding:
-
- Free publication
- Verified by:
- Gdańsk University of Technology
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