Author:
Naon Deborah,Zaninello Marta,Giacomello Marta,Varanita Tatiana,Grespi Francesca,Lakshminaranayan Sowmya,Serafini Annalisa,Semenzato Martina,Herkenne Stephanie,Hernández-Alvarez Maria Isabel,Zorzano Antonio,De Stefani Diego,Dorn Gerald W.,Scorrano Luca
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.
Funder
Fondazione Telethon
Associazione Italiana per la Ricerca sul Cancro
EC | European Research Council
Ministero dell'Istruzione, dell'Università e della Ricerca
European Commission Directorate-General for Research and Innovation
National Heart and Lung Institute
Ministerio de Economía y Competitividad
Ministry of Economy and Competitiveness | Instituto de Salud Carlos III
Publisher
Proceedings of the National Academy of Sciences
Cited by
383 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献