Publication Date:
2008-12-05
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉de Brito, Olga Martins -- Scorrano, Luca -- TCR07002/Telethon/Italy -- England -- Nature. 2008 Dec 4;456(7222):605-10. doi: 10.1038/nature07534.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Dulbecco-Telethon Institute, Venetian Institute of Molecular Medicine, Via Orus 2, 35129 Padova, Italy.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19052620" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Calcium/metabolism
;
Calcium Signaling
;
Charcot-Marie-Tooth Disease/genetics
;
Endoplasmic Reticulum/*metabolism
;
Fibroblasts
;
GTP Phosphohydrolases/deficiency/genetics/*metabolism
;
HeLa Cells
;
Humans
;
Inositol 1,4,5-Trisphosphate/metabolism
;
Membrane Proteins/deficiency/genetics/*metabolism
;
Mice
;
Mitochondria/*metabolism
;
Mitochondrial Proteins/deficiency/genetics/*metabolism
;
Organelle Shape
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
