CMT 2A : Mitofusin 2 tethers endoplasmic reticulum to mitochondria

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Nature. 2008 Dec 4;456(7222):605-10.

Mitofusin 2 tethers endoplasmic reticulum to mitochondria.

de Brito OM, Scorrano L.

Dulbecco-Telethon Institute, Venetian Institute of Molecular

Medicine, Via Orus 2, 35129 Padova, Italy.

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.