Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 113, Issue 40, Pages 11249-11254Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1606786113
Keywords
mitochondria; Mfn2; Ca2(+); tethering; interorganellar communication
Categories
Funding
- Telethon-Italy Grant [GGP12162, GGP15198, TCR02016]
- Associazione Italiana per la Ricerca sul Cancro Italy
- European Research Council [FP7-282280, FP7 CIG PCIG13-GA-2013-618697]
- Ministero dell'Istruzione, dell'Universita e della Ricerca Fondo per gli Investimenti della Ricerca di Base [RBAP11Z3YA_005]
- National Heart, Lung, and Blood Institute [R01 HL59888, R01 108943, R01 128071]
- Ministry of Economy and Competitiveness Grant [SAF2013-40987R]
- Generalitat de Catalunya [2014SGR48]
- Institucio Catalana de Recerca i Estudis Avancats Academia
- Centro de Investigacion Biomedica en Red de Diabetes y Enfermedades Metabolicas Asociadas
- Instituto de Salud Carlos III [PIE14/00045]
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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.
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