Cited by 2,442Mitochondrial Function and PathologyIon Channels and ReceptorsAutophagy in Disease and Therapy

Mitofusin 2 tethers endoplasmic reticulum to mitochondria

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de Brito, Olga Martins, Scorrano, Luca·2008·Nature

Abstract

Juxtaposition between endoplasmic reticulum (ER) and mitochondria is a common structural feature, providing the physical basis for intercommunication during Ca(2+) signalling; yet, the molecular mechanisms controlling this interaction are unknown. Here we show that mitofusin 2, a mitochondrial dynamin-related protein mutated in the inherited motor neuropathy Charcot-Marie-Tooth type IIa, is enriched at the ER-mitochondria interface. Ablation or silencing of mitofusin 2 in mouse embryonic fibroblasts and HeLa cells disrupts ER morphology and loosens ER-mitochondria interactions, thereby reducing the efficiency of mitochondrial Ca(2+) uptake in response to stimuli that generate inositol-1,4,5-trisphosphate. An in vitro assay as well as genetic and biochemical evidences support a model in which mitofusin 2 on the ER bridges the two organelles by engaging in homotypic and heterotypic complexes with mitofusin 1 or 2 on the surface of mitochondria. Thus, mitofusin 2 tethers ER to mitochondria, a juxtaposition required for efficient mitochondrial Ca(2+) uptake.

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Crossref · 10.1038/nature07534

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Authors
de Brito, O. M., & Scorrano, L.
Affiliations
University of Geneva (CH)
Corresponding author
Scorrano, Luca
Venue
Nature
Published
2008-12-01
Volume
456
Issue
7222
Pages
605-610
ISSN
  • 0028-0836 (ISSN-L)
  • 1476-4687
OpenAlex
W2166432730
Cited by
2,442
References
35
Citations by year
2026: 105 · 2025: 142 · 2024: 136 · 2023: 142 · 2022: 139 · 2021: 188 · 2020: 186 · 2019: 148 · 2018: 132 · 2017: 175 · 2016: 129 · 2015: 119 · 2014: 132 · 2013: 133 · 2012: 145
FWCI
39.45
Type
journal article
Language
en
Open access
Locations
  • Nature (publishedVersion)
  • PubMed (publishedVersion)
  • Archive ouverte UNIGE (University of Geneva) (submittedVersion, cc-by)
  • RePEc: Research Papers in Economics (submittedVersion)
  • Padua Research Archive (University of Padova) (submittedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
  • Life Sciences › Neuroscience › Sensory Systems › Ion Channels and Receptors
  • Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
Keywords
mitofusin 2, mitochondrial calcium uptake, inositol 1,4,5-trisphosphate, calcium signaling, dynamin-related proteins, ER morphology, calcium homeostasis
MeSH terms
Animals, Calcium, Charcot-Marie-Tooth Disease, Endoplasmic Reticulum, Fibroblasts, HeLa Cells, Humans, Membrane Proteins, Mitochondria, Inositol 1,4,5-Trisphosphate, Calcium Signaling, GTP Phosphohydrolases, Mitochondrial Proteins, Mice, Organelle Shape

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