Guo, C., Wilkinson, K.A., Evans, A.J. et al. (2 more authors) (2017) SENP3-mediated deSUMOylation of Drp1 facilitates interaction with Mff to promote cell death. Scientific Reports, 7. 43811. p. 43811. ISSN 2045-2322
Abstract
The GTPase dynamin-related protein 1 (Drp1) is essential for physiological and pathophysiological mitochondrial fission. DeSUMOylation of Drp1 by the enzyme SENP3 promotes cell death during reperfusion after ischaemia by enhancing Drp1 partitioning to the mitochondrial outer membrane (MOM), which causes cytochrome c release and apoptosis. However, how deSUMOylation recruits Drp1 to the MOM is unknown. Here we show that deSUMOylation selectively promotes Drp1 binding to the MOM resident adaptor protein mitochondrial fission factor (Mff). Consistent with this, preventing Drp1 SUMOylation by mutating the SUMO acceptor sites enhances binding to Mff. Conversely, increasing Drp1 SUMOylation by knocking down SENP3 reduces both Drp1 binding to Mff and stress-induced cytochrome c release. Directly tethering Drp1 to the MOM bypasses the need for Mff to evoke cytochrome c release, and occludes the effect of SENP3 overexpression. Thus, Drp1 deSUMOylation promotes cell death by enhancing Mff-mediated mitochondrial recruitment. These data provide a mechanistic explanation for how the SUMOylation status of Drp1 acts as a key switch in cell death/survival decisions following extreme cell stress.
Metadata
Item Type: | Article |
---|---|
Authors/Creators: |
|
Copyright, Publisher and Additional Information: | This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
Dates: |
|
Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Science (Sheffield) > School of Biosciences (Sheffield) > Department of Biomedical Science (Sheffield) |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 14 Mar 2017 09:44 |
Last Modified: | 14 Mar 2017 09:44 |
Published Version: | https://doi.org/10.1038/srep43811 |
Status: | Published |
Publisher: | Nature Publishing Group |
Refereed: | Yes |
Identification Number: | 10.1038/srep43811 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:113427 |
Downloads
Filename: srep43811-1.pdf
Licence: CC-BY 4.0
Filename: srep43811-s1.pdf
Licence: CC-BY 4.0