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The WD40 protein Caf4p is a component of the mitochondrial fission machinery and recruits Dnm1p to mitochondria

Griffin, Erik E. and Graumann, Johannes and Chan, David C. (2005) The WD40 protein Caf4p is a component of the mitochondrial fission machinery and recruits Dnm1p to mitochondria. Journal of Cell Biology, 170 (2). pp. 237-248. ISSN 0021-9525. http://resolver.caltech.edu/CaltechAUTHORS:GRIjcb05

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Abstract

The mitochondrial division machinery regulates mitochondrial dynamics and consists of Fis1p, Mdv1p, and Dnm1p. Mitochondrial division relies on the recruitment of the dynamin-related protein Dnm1p to mitochondria. Dnm1p recruitment depends on the mitochondrial outer membrane protein Fis1p. Mdv1p interacts with Fis1p and Dnm1p, but is thought to act at a late step during fission because Mdv1p is dispensable for Dnm1p localization. We identify the WD40 repeat protein Caf4p as a Fis1p-associated protein that localizes to mitochondria in a Fis1p-dependent manner. Caf4p interacts with each component of the fission apparatus: with Fis1p and Mdv1p through its NH2-terminal half and with Dnm1p through its COOH-terminal WD40 domain. We demonstrate that mdv1{Delta} yeast contain residual mitochondrial fission due to the redundant activity of Caf4p. Moreover, recruitment of Dnm1p to mitochondria is disrupted in mdv1{Delta} caf4{Delta} yeast, demonstrating that Mdv1p and Caf4p are molecular adaptors that recruit Dnm1p to mitochondrial fission sites. Our studies support a revised model for assembly of the mitochondrial fission apparatus.


Item Type:Article
Additional Information:© The Rockefeller University Press, 2005 Submitted: 25 March 2005; Accepted: 9 June 2005; Published online July 11, 2005. doi:10.1083/jcb.200503148 We thank T.R. Suntoke, S.A. Detmer, and H. Chen for helpful comments on the manuscript; and L. Lytle for technical assistance. J. Copeland constructed some of the two-hybrid plasmids. We thank Dr. Ray Deshaies for stimulating discussions on mass spectrometry. E.E. Griffin was supported by a National Institutes of Health training grant (NIH GM07616) and a Ferguson fellowship. MudPIT analysis was performed in the mass spectrometry facility of the laboratory of R.J. Deshaies (Investigator, Howard Hughes Medical Institute, Caltech). This facility is supported by the Beckman Institute at Caltech and by a grant from the Department of Energy to R.J. Deshaies and B.J. Wold. J. Graumann is supported by R.J. Deshaies through Howard Hughes Medical Institute funds. D.C. Chan is a Bren Scholar and Beckman Young Investigator. This research was supported by the National Institutes of Health (GM62967). Table S1 lists proteins identified in MudPIT experiments with M9TH-Fis1p. Table S2 shows yeast strains. Table S3 lists primer sequences. Videos 1 and 2 show mitochondrial fission in mdv1{Delta} yeast. Mitochondria were monitored by the mitochondrial outer membrane marker OM45-GFP. Arrows highlight a subset of fission events. Online supplemental material available at http://www.jcb.org/cgi/content/full/jcb.200503148/DC1.
Record Number:CaltechAUTHORS:GRIjcb05
Persistent URL:http://resolver.caltech.edu/CaltechAUTHORS:GRIjcb05
Alternative URL:http://dx.doi.org/10.1083/jcb.200503148
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ID Code:5315
Collection:CaltechAUTHORS
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Deposited On:09 Oct 2006
Last Modified:26 Dec 2012 09:05

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