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The Mitochondrial Fission Receptor MiD51 Requires ADP as a Cofactor

Losón, Oliver C. and Liu, Raymond and Rome, Michael E. and Meng, Shuxia and Kaiser, Jens T. and Shan, Shu-ou and Chan, David C. (2014) The Mitochondrial Fission Receptor MiD51 Requires ADP as a Cofactor. Structure, 22 (3). pp. 367-377. ISSN 0969-2126. PMCID PMC4066849. http://resolver.caltech.edu/CaltechAUTHORS:20140214-120458864

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Abstract

Mitochondrial fission requires recruitment of dynamin- related protein 1 (Drp1) to the mitochondrial surface and activation of its GTP-dependent scission function. The Drp1 receptors MiD49 and MiD51 recruit Drp1 to facilitate mitochondrial fission, but their mechanism of action is poorly understood. Using X-ray crystallography, we demonstrate that MiD51 contains a nucleotidyl transferase domain that binds ADP with high affinity. MiD51 recruits Drp1 via a surface loop that functions independently of ADP binding. However, in the absence of nucleotide binding, the recruited Drp1 cannot be activated for fission. Purified MiD51 strongly inhibits Drp1 assembly and GTP hydrolysis in the absence of ADP. Addition of ADP relieves this inhibition and promotes Drp1 assembly into spirals with enhanced GTP hydrolysis. Our results reveal ADP as an essential cofactor for MiD51 during mitochondrial fission.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1016/j.str.2014.01.001DOIArticle
http://www.sciencedirect.com/science/article/pii/S0969212614000057PublisherArticle
http://www.cell.com/structure/abstract/S0969-2126(14)00005-7PublisherArticle
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4066849/PubMed CentralArticle
ORCID:
AuthorORCID
Shan, Shu-ou0000-0002-6526-1733
Additional Information:© 2014 Elsevier Ltd. Received: December 31, 2013; Revised: December 31, 2013 Accepted: January 2, 2014; Published: February 6, 2014. Supplemental Information includes five figures and can be found with this article online at http://dx.doi.org/10.1016/j.str.2014.01.001. We are grateful to Meera Rao for assistance with the GTPase assay and Alasdair McDowell for guidance with EM. We thank the Beckman Foundation at Caltech for support of the EM resource and the Gordon and Betty Moore Foundation and Augoron Institute for support of the Grant Jensen lab microscopy center. We acknowledge the Gordon and Betty Moore Foundation, the Beckman Institute, and the Sanofi-Aventis Bioengineering Research Program at Caltech for their generous support of the Molecular Observatory at Caltech. Operations at SSRL are supported by the US Department of Energy and the National Institutes of Health (NIH). This work was supported by a grant from the NIH (GM062967). O.C.L. was supported by an R. L. Kirschstein National Research Service Award (5F31GM089327) and an American Physiological Society William Townsend Porter predoctoral fellowship. PDB Accession Numbers: 4OAF (native structure), 4OAG (bound to ADP), 4OAH (H201A mutant structure), 4OAI (dimer mutant structure)
Funders:
Funding AgencyGrant Number
Gordon and Betty Moore FoundationUNSPECIFIED
Caltech Beckman Institute UNSPECIFIED
Caltech Sanofi-Aventis Bioengineering Research ProgramUNSPECIFIED
NIHGM062967
NIH Predoctoral Fellowship5F31GM089327
American Physiological Society William Townsend Porter Predoctoral FellowshipUNSPECIFIED
PubMed Central ID:PMC4066849
Record Number:CaltechAUTHORS:20140214-120458864
Persistent URL:http://resolver.caltech.edu/CaltechAUTHORS:20140214-120458864
Official Citation:Losón et al., The Mitochondrial Fission Receptor MiD51 Requires ADP as a Cofactor, Structure (2014), http:// dx.doi.org/10.1016/j.str.2014.01.001
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:43840
Collection:CaltechAUTHORS
Deposited By: Aucoeur Ngo
Deposited On:14 Feb 2014 20:44
Last Modified:21 Jul 2017 22:36

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