Mitofusin 2 tethers endoplasmic reticulum to mitochondria

作者：de Brito Olga Martins; Scorrano Luca^*

来源：Nature, 2008, 456(7222): 605-U47.

DOI：10.1038/nature07534

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.

• 出版日期2008-12-4