Mitofusion 2 tethers endoplasmic reticulum to mitochondria (Nature, 2008, 456:605-610)

報告日期: 2009/05/05
報告時間: 16:05/16:55
報告學生: 鄭蕙芬(英文報告)
講評老師: 林秋烽

Mitofusin 2 tethers endoplasmic reticulum to mitochondria

Olga Martins de Brito and Luca Scorrano, 2008 Nature 456: 605-611


Speaker: Huei-Fen Jheng

Commentator: Dr. Chiou-Feng Lin

Date: 2009/05/05

Place: 602 room

Time: 16:05-16:55


Endoplasmic reticulum (ER)-mitochondria tethering, a physical association between the ER and mitochondria, has important roles in various cellular function. One of its functions is to mediate mitochondria uptake of released Ca2+ from ER, ultimately affecting organelle metabolism and the response to Ca2+–dependent death stimuli. However, the molecular mechanisms controlling this interaction are still unknown. Mitofusin 2 (Mfn2), located on the mitochondrial outer membrane, is critical for mitochondrial fusion, as well as intrinsic cell death. The authors hypothesized that Mfn2 was required for tethering of ER and mitochondria. In this study, the authors used sucrose gradient centrifugation to separate subcellular fraction, and confocal imaging to indicate the colocalization between ER and mitochondria. They showed that Mfn2 was enriched at contact sites between ER and mitochondria. Ablation or silence of Mfn2 in mouse embryonic fibroblast and HeLa cell disrupted ER morphology and reduced ER-mitochondria interactions. Genetic and biochemical evidences indicated that Mfn2 on ER required either Mfn1 or Mfn2 on mitochondria to bridge these two organelles. Furthermore, the data indicated that Ca2+ uptake was significantly slower when mitochondria from Mfn2-/- cells were exposed to the same Ca2+ concentration in cytosol. In conclusion, Mfn2 regulated the ER-mitochondria tethers, by engaging homo- and hetero-complexes comprising Mfn2 at the ER and Mfn2 or Mfn1 on mitochondria, and played a role for efficient mitochondrial Ca2+ uptake.



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