Mitofusin 2 tethers endoplasmic reticulum to mitochondria
Authors: Luca Scorrano
Olga Martins de Brito
Journal: Nature (2008)
Discipline: Multidisciplinary
Keywords: endoplasmic reticulum; mitochondria; mitofusin 2; Ca(2+) signalling; Charcot-Marie-Tooth type IIa
Affiliations: Dulbecco-Telethon Institute, Venetian Institute of Molecular Medicine, Via Orus 2, 35129 Padova, Italy.

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. 

Retracted: No

PubPeer comments:
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 Revisiting an old discussion, because this paper appears to have some serious issues and only one of them was addressed in the Corrigendum. Here are the concerns mentioned above that I can confirm, and an additional one. * Figure 1A: Two panels appear to be showing the same cell. It is not a simple duplication. The image has been rotated and the contrast has been changed. This concern has been addressed in the Corrigendum. Discussed above in #1. Marked with red boxes. ![file] * Figure 2F. First discussed above in #3. The three blank Supernatant panels look identical to each other. Enhancing the contrast, I can confirm this. There are clear signals here that are not random, and that cannot be attributed to compression artifacts. I see a slanted darker line and a light spot in the middle, a  footstep in the top left, and a dark spot in the bottom right corner. The three panels that look identical are here with green boxes. ![file] * Figure 4B. The middle and right panels appear to be showing some similarities. Marked by me in light blue. These could be caused by stripping and reprobing the same blot, so although I agree with the similarities, this might not be a problem. I am posting the image here because it is not showing up in Comment #1. ![file] * Figure S3C. A potential new concern. The a-TOM20 LM panel appears to look similar to the a-SERCA2 mito panel. Shown here with aqua boxes. Contrast enhanced to bring out details. These do not look like compression artifacts to me; they are not blocky, and appear to show a real background signal. ![file] * Figure S9. Raised above in comment #5. The bottom left part of the right panel in Figure S9C looks similar to the bottom right part of the right panel in Figure S9C. They are supposed to show different samples. Marked here in orange. ![file] ,