title: Critical reappraisal confirms that Mitofusin 2 is an endoplasmic reticulum-mitochondria tether.
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.
authors.affiliation: Department of Biology, University of Padua, 35121 Padua, Italy; Department of Biomedical Sciences, University of Padua, 35121 Padua, Italy.
authors.forename: Deborah
authors.initials: D
authors.lastname: Naon
authors.affiliation: Department of Biology, University of Padua, 35121 Padua, Italy; Dulbecco-Telethon Institute, Venetian Institute of Molecular Medicine, 35129 Padua, Italy; Fondazione S. Lucia Istituto di Ricovero e Cura a Carattere Scientifico, 00161 Rome, Italy.
authors.forename: Marta
authors.initials: M
authors.lastname: Zaninello
authors.affiliation: Department of Biology, University of Padua, 35121 Padua, Italy; Dulbecco-Telethon Institute, Venetian Institute of Molecular Medicine, 35129 Padua, Italy.
authors.forename: Marta
authors.initials: M
authors.lastname: Giacomello
authors.affiliation: Department of Biology, University of Padua, 35121 Padua, Italy; Dulbecco-Telethon Institute, Venetian Institute of Molecular Medicine, 35129 Padua, Italy.
authors.forename: Tatiana
authors.initials: T
authors.lastname: Varanita
authors.affiliation: Department of Biology, University of Padua, 35121 Padua, Italy; Dulbecco-Telethon Institute, Venetian Institute of Molecular Medicine, 35129 Padua, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Grespi
authors.affiliation: Department of Biology, University of Padua, 35121 Padua, Italy; Fondazione S. Lucia Istituto di Ricovero e Cura a Carattere Scientifico, 00161 Rome, Italy.
authors.forename: Sowmya
authors.initials: S
authors.lastname: Lakshminaranayan
authors.affiliation: Department of Biology, University of Padua, 35121 Padua, Italy; Dulbecco-Telethon Institute, Venetian Institute of Molecular Medicine, 35129 Padua, Italy.
authors.forename: Annalisa
authors.initials: A
authors.lastname: Serafini
authors.affiliation: Department of Biology, University of Padua, 35121 Padua, Italy; Dulbecco-Telethon Institute, Venetian Institute of Molecular Medicine, 35129 Padua, Italy.
authors.forename: Martina
authors.initials: M
authors.lastname: Semenzato
authors.affiliation: Department of Biology, University of Padua, 35121 Padua, Italy; Dulbecco-Telethon Institute, Venetian Institute of Molecular Medicine, 35129 Padua, Italy.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Herkenne
authors.affiliation: Institute for Research in Biomedicine, 08028 Barcelona, Spain.
authors.forename: Maria Isabel
authors.initials: MI
authors.lastname: Hernández-Alvarez
authors.affiliation: Institute for Research in Biomedicine, 08028 Barcelona, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Zorzano
authors.affiliation: Department of Biomedical Sciences, University of Padua, 35121 Padua, Italy.
authors.forename: Diego
authors.initials: D
authors.lastname: De Stefani
authors.affiliation: Department of Internal Medicine, Center for Pharmacogenomics, Washington University School of Medicine, St. Louis, MO 63110.
authors.forename: Gerald W
authors.initials: GW
authors.lastname: Dorn
authors.affiliation: Department of Biology, University of Padua, 35121 Padua, Italy; Dulbecco-Telethon Institute, Venetian Institute of Molecular Medicine, 35129 Padua, Italy; luca.scorrano@unipd.it.
authors.forename: Luca
authors.initials: L
authors.lastname: Scorrano
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000378:metabolism; D004622:Embryo, Mammalian / Q000166:cytology; D004721:Endoplasmic Reticulum / Q000378:metabolism* / Q000648:ultrastructure; D005347:Fibroblasts / Q000378:metabolism / Q000648:ultrastructure; D020558:GTP Phosphohydrolases / Q000378:metabolism*; D017353:Gene Deletion; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism; D006801:Humans; D008099:Liver / Q000378:metabolism; D018345:Mice, Knockout; D008928:Mitochondria / Q000378:metabolism* / Q000648:ultrastructure; D015335:Molecular Probes / Q000378:metabolism
chemical_list: D015220:Calcium Channels; D015335:Molecular Probes; C034703:mitochondrial calcium uniporter; D020558:GTP Phosphohydrolases; C488751:Mfn2 protein, mouse; D002118:Calcium
keywords: Ca2+; Mfn2; interorganellar communication; mitochondria; tethering