Cancer-Related NEET Proteins Transfer 2Fe-2S Clusters to Anamorsin, a Protein Required for Cytosolic Iron-Sulfur Cluster Biogenesis

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dc.citation.firstpagee0139699en_US
dc.citation.issueNumber10en_US
dc.citation.journalTitlePLoS Oneen_US
dc.citation.volumeNumber10en_US
dc.contributor.authorLipper, Colin H.en_US
dc.contributor.authorPaddock, Mark L.en_US
dc.contributor.authorOnuchic, José N.en_US
dc.contributor.authorMittler, Ronen_US
dc.contributor.authorNechushtai, Rachelen_US
dc.contributor.authorJennings, Patricia A.en_US
dc.contributor.orgCenter for Theoretical Biological Physicsen_US
dc.date.accessioned2016-01-15T19:47:52Zen_US
dc.date.available2016-01-15T19:47:52Zen_US
dc.date.issued2015en_US
dc.description.abstractIron-sulfur cluster biogenesis is executed by distinct protein assembly systems. Mammals have two systems, the mitochondrial Fe-S cluster assembly system (ISC) and the cytosolic assembly system (CIA), that are connected by an unknown mechanism. The human members of the NEET family of 2Fe-2S proteins, nutrient-deprivation autophagy factor-1 (NAF-1) and mitoNEET (mNT), are located at the interface between the mitochondria and the cytosol. These proteins have been implicated in cancer cell proliferation, and they can transfer their 2Fe-2S clusters to a standard apo-acceptor protein. Here we report the first physiological 2Fe-2S cluster acceptor for both NEET proteins as human Anamorsin (also known as cytokine induced apoptosis inhibitor-1; CIAPIN-1). Anamorsin is an electron transfer protein containing two iron-sulfur cluster-binding sites that is required for cytosolic Fe-S cluster assembly. We show, using UV-Vis spectroscopy, that both NAF-1 and mNT can transfer their 2Fe-2S clusters to apo-Anamorsin with second order rate constants similar to those of other known human 2Fe-2S transfer proteins. A direct protein-protein interaction of the NEET proteins with apo-Anamorsin was detected using biolayer interferometry. Furthermore, electrospray mass spectrometry of holo-Anamorsin prepared by cluster transfer shows that it receives both of its 2Fe-2S clusters from the NEETs. We propose that mNT and NAF-1 can provide parallel routes connecting the mitochondrial ISC system and the CIA. 2Fe-2S clusters assembled in the mitochondria are received by NEET proteins and when needed transferred to Anamorsin, activating the CIA.en_US
dc.identifier.citationLipper, Colin H., Paddock, Mark L., Onuchic, José N., et al.. "Cancer-Related NEET Proteins Transfer 2Fe-2S Clusters to Anamorsin, a Protein Required for Cytosolic Iron-Sulfur Cluster Biogenesis." <i>PLoS One,</i> 10, no. 10 (2015) Public Library of Science: e0139699. http://dx.doi.org/10.1371/journal.pone.0139699.en_US
dc.identifier.doihttp://dx.doi.org/10.1371/journal.pone.0139699en_US
dc.identifier.urihttps://hdl.handle.net/1911/87857en_US
dc.language.isoengen_US
dc.publisherPublic Library of Scienceen_US
dc.rightsThis is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.en_US
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en_US
dc.titleCancer-Related NEET Proteins Transfer 2Fe-2S Clusters to Anamorsin, a Protein Required for Cytosolic Iron-Sulfur Cluster Biogenesisen_US
dc.typeJournal articleen_US
dc.type.dcmiTexten_US
dc.type.publicationpublisher versionen_US
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