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Title

Mitofusin 2 tethers endoplasmic reticulum to mitochondria

Authors
Martins de Brito, Olga
Published in Nature. 2008, vol. 456, no. 7222, p. 605-10
Abstract Juxtaposition between endoplasmic reticulum (ER) and mitochondria is a common structural feature, providing the physical basis for intercommunication during Ca(2+) signalling; yet, the molecular mechanisms controlling this interaction are unknown. Here we show that mitofusin 2, a mitochondrial dynamin-related protein mutated in the inherited motor neuropathy Charcot-Marie-Tooth type IIa, is enriched at the ER-mitochondria interface. Ablation or silencing of mitofusin 2 in mouse embryonic fibroblasts and HeLa cells disrupts ER morphology and loosens ER-mitochondria interactions, thereby reducing the efficiency of mitochondrial Ca(2+) uptake in response to stimuli that generate inositol-1,4,5-trisphosphate. An in vitro assay as well as genetic and biochemical evidences support a model in which mitofusin 2 on the ER bridges the two organelles by engaging in homotypic and heterotypic complexes with mitofusin 1 or 2 on the surface of mitochondria. Thus, mitofusin 2 tethers ER to mitochondria, a juxtaposition required for efficient mitochondrial Ca(2+) uptake.
Keywords AnimalsCalcium/metabolismCalcium SignalingCharcot-Marie-Tooth Disease/geneticsEndoplasmic Reticulum/metabolismFibroblastsGTP Phosphohydrolases/deficiency/genetics/metabolismHela CellsHumansInositol 1,4,5-Trisphosphate/metabolismMembrane Proteins/deficiency/genetics/metabolismMiceMitochondria/metabolismMitochondrial Proteins/deficiency/genetics/metabolismOrganelle Shape
Identifiers
PMID: 19052620
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Structures
Research group Les mitochondries dans la vie cellulaire (850)
Citation
(ISO format)
MARTINS DE BRITO, Olga, SCORRANO, Luca. Mitofusin 2 tethers endoplasmic reticulum to mitochondria. In: Nature, 2008, vol. 456, n° 7222, p. 605-10. https://archive-ouverte.unige.ch/unige:2381

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Deposited on : 2009-08-10

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