Critical reappraisal confirms that Mitofusin 2 is an endoplasmic reticulum-mitochondria tether

Deborah Naon, Marta Zaninello, Marta Giacomello, Tatiana Varanita, Francesca Grespi, Sowmya Lakshminaranayan, Annalisa Serafini, Martina Semenzato, Stephanie Herkenne, Maria Isabel Hernández-Alvarez, Antonio Zorzano, Diego De Stefani, Gerald W. Dorn, Luca Scorrano

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176 Scopus citations

Abstract

The discovery of the multiple roles of mitochondria-endoplasmic reticulum (ER) juxtaposition in cell biology often relied upon the exploitation of Mitofusin (Mfn) 2 as an ER-mitochondria tether. However, this established Mfn2 function was recently questioned, calling for a critical re-evaluation of Mfn2's role in ER-mitochondria cross-talk. Electron microscopy and fluorescence-based probes of organelle proximity confirmed that ER-mitochondria juxtaposition was reduced by constitutive or acute Mfn2 deletion. Functionally, mitochondrial uptake of Ca2+ released from the ER was reduced following acute Mfn2 ablation, as well as in Mfn2-/- cells overexpressing the mitochondrial calcium uniporter. Mitochondrial Ca2+ uptake rate and extent were normal in isolated Mfn2-/- liver mitochondria, consistent with the finding that acute or chronic Mfn2 ablation or overexpression did not alter mitochondrial calcium uniporter complex component levels. Hence, Mfn2 stands as a bona fide ER-mitochondria tether whose ablation decreases interorganellar juxtaposition and communication.

Original languageEnglish
Pages (from-to)11249-11254
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume113
Issue number40
DOIs
StatePublished - Oct 4 2016

Keywords

  • Ca
  • Interorganellar communication
  • Mfn2
  • Mitochondria
  • Tethering

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    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. (2016). Critical reappraisal confirms that Mitofusin 2 is an endoplasmic reticulum-mitochondria tether. Proceedings of the National Academy of Sciences of the United States of America, 113(40), 11249-11254. https://doi.org/10.1073/pnas.1606786113