Critical reappraisal confirms that Mitofusin 2 is an endoplasmic reticulum–mitochondria tether
Open accessAbstract
Significance: Organelles engage in heterotypic interactions crucial for metabolic and signaling cascades. The best-studied case of this heterotypic interaction is that between the mitochondria and endoplasmic reticulum (ER), crucial for transfer of lipids and especially Ca 2+ between the two organelles. The original discovery that the mitochondria-shaping protein Mitofusin 2 (Mfn2) physically tethers the ER to mitochondria was recently challenged. Here, electron microscopy and fluorescent probes of organelle proximity provide definitive evidence that constitutive or acute Mfn2 ablation increases the distance between the ER and mitochondria. Functionally, this process reduces mitochondrial Ca 2+ uptake without altering the mitochondrial Ca 2+ uniporter complex in multiple tissues. Thus, the discoveries of the role of ER–mitochondria juxtaposition in cell biology based on Mfn2 as a tool remain unchallenged.
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MFN2, but not MFN1, is expressed on mitochondria-associated endoplasmic reticulum membranes (MAM) and to a lesser extent on ER/SR.
“MFN2, and not MFN1, is expressed on the mitochondria-associated endoplasmic reticulum membranes (MAM) and, to a lesser extent, to the endoplasmic/sarcoplasmic reticulum (ER/SR) [63, 64].”
From The connection between the dynamic remodeling of the mitochondrial network and the regulation of muscle mass (2021) · cites this paper as [64]
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“Cells were co-transfected with ZnT9-50Met or ZnT9-50Val plasmids and a modified FRET-based ER-mitochondria proximity probe named FEMP [71].”
- Authors
- Naon, D., Zaninello, M., Giacomello, M., Varanita, T., Grespi, F., Lakshminaranayan, S., Serafini, A., Semenzato, M., Herkenne, S., Hernández-Alvarez, M. I., Zorzano, A., De Stefani, D., Dorn, G. W., & Scorrano, L.
- Affiliations
- Department of Biology, University of Padua, 35121 Padua, Italy;
- University of Padua (IT)
- Institute for Research in Biomedicine, 08028 Barcelona, Spain;
- Department of Biomedical Sciences, University of Padua, 35121 Padua, Italy;
- Washington University in St. Louis (US)
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2016-09-19
- Volume
- 113
- Issue
- 40
- Pages
- 11249-11254
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC5056088
- OpenAlex
- W2521680809
- Cited by
- 521
- References
- 41
- Citations by year
- 2026: 45 · 2025: 45 · 2024: 43 · 2023: 42 · 2022: 54 · 2021: 64 · 2020: 71 · 2019: 55 · 2018: 44 · 2017: 55 · 2016: 2
- FWCI
- 27.03
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Open Repository and Bibliography (University of Liège) (submittedVersion)
- Padua Research Archive (University of Padova) (submittedVersion)
- Funders
- Fondazione Telethon (GGP12162, GGP15198, TCR02016)
- Associazione Italiana per la Ricerca sul Cancro (IG11716)
- EC | European Research Council (FP7-282280)
- Ministero dell'Istruzione, dell'Università e della Ricerca (FIRB RBAP11Z3YA_005)
- European Commission Directorate-General for Research and Innovation (PCIG13-GA-2013-618697)
- National Heart and Lung Institute (HL59888, 108943, 128071)
- Ministerio de Economía y Competitividad (SAF2013-40987R)
- Ministry of Economy and Competitiveness | Instituto de Salud Carlos III (PIE14/00045)
- 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, mitochondrial calcium uniporter, lipid transfer, mitochondrial morphology
- MeSH terms
- Animals, Calcium, Embryo, Mammalian, Endoplasmic Reticulum, Fibroblasts, Humans, Liver, Mitochondria, Calcium Channels, Molecular Probes, Gene Deletion, Mice, Knockout, GTP Phosphohydrolases, Human Umbilical Vein Endothelial Cells
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