A VDAC1-mediated NEET protein chain transfers [2Fe-2S] clusters between the mitochondria and the cytosol and impacts mitochondrial dynamics

Simple item page
dc.citation.articleNumbere2121491119en_US
dc.citation.issueNumber7en_US
dc.citation.journalTitleProceedings of the National Academy of Sciencesen_US
dc.citation.volumeNumber119en_US
dc.contributor.authorKarmi, Olaen_US
dc.contributor.authorMarjault, Henri-Baptisteen_US
dc.contributor.authorBai, Fangen_US
dc.contributor.authorRoy, Susmitaen_US
dc.contributor.authorSohn, Yang-Sungen_US
dc.contributor.authorYahana, Merav Darashen_US
dc.contributor.authorMorcos, Farucken_US
dc.contributor.authorIoannidis, Konstantinosen_US
dc.contributor.authorNahmias, Yaakoven_US
dc.contributor.authorJennings, Patricia A.en_US
dc.contributor.authorMittler, Ronen_US
dc.contributor.authorOnuchic, José N.en_US
dc.contributor.authorNechushtai, Rachelen_US
dc.contributor.orgCenter for Theoretical Biological Physicsen_US
dc.date.accessioned2022-03-24T13:31:45Zen_US
dc.date.available2022-03-24T13:31:45Zen_US
dc.date.issued2022en_US
dc.description.abstractMitochondrial inner NEET (MiNT) and the outer mitochondrial membrane (OMM) mitoNEET (mNT) proteins belong to the NEET protein family. This family plays a key role in mitochondrial labile iron and reactive oxygen species (ROS) homeostasis. NEET proteins contain labile [2Fe-2S] clusters which can be transferred to apo-acceptor proteins. In eukaryotes, the biogenesis of [2Fe-2S] clusters occurs within the mitochondria by the iron–sulfur cluster (ISC) system; the clusters are then transferred to [2Fe-2S] proteins within the mitochondria or exported to cytosolic proteins and the cytosolic iron–sulfur cluster assembly (CIA) system. The last step of export of the [2Fe-2S] is not yet fully characterized. Here we show that MiNT interacts with voltage-dependent anion channel 1 (VDAC1), a major OMM protein that connects the intermembrane space with the cytosol and participates in regulating the levels of different ions including mitochondrial labile iron (mLI). We further show that VDAC1 is mediating the interaction between MiNT and mNT, in which MiNT transfers its [2Fe-2S] clusters from inside the mitochondria to mNT that is facing the cytosol. This MiNT–VDAC1–mNT interaction is shown both experimentally and by computational calculations. Additionally, we show that modifying MiNT expression in breast cancer cells affects the dynamics of mitochondrial structure and morphology, mitochondrial function, and breast cancer tumor growth. Our findings reveal a pathway for the transfer of [2Fe-2S] clusters, which are assembled inside the mitochondria, to the cytosol.en_US
dc.identifier.citationKarmi, Ola, Marjault, Henri-Baptiste, Bai, Fang, et al.. "A VDAC1-mediated NEET protein chain transfers [2Fe-2S] clusters between the mitochondria and the cytosol and impacts mitochondrial dynamics." <i>Proceedings of the National Academy of Sciences,</i> 119, no. 7 (2022) National Academy of Sciences: https://doi.org/10.1073/pnas.2121491119.en_US
dc.identifier.digitalpnas-2121491119en_US
dc.identifier.doihttps://doi.org/10.1073/pnas.2121491119en_US
dc.identifier.urihttps://hdl.handle.net/1911/112055en_US
dc.language.isoengen_US
dc.publisherNational Academy of Sciencesen_US
dc.rightsThis article is distributed under Creative Commons Attribution-NonCommercialNoDerivatives License 4.0 (CC BY-NC-ND).en_US
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/en_US
dc.titleA VDAC1-mediated NEET protein chain transfers [2Fe-2S] clusters between the mitochondria and the cytosol and impacts mitochondrial dynamicsen_US
dc.typeJournal articleen_US
dc.type.dcmiTexten_US
dc.type.publicationpublisher versionen_US
Files
Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
pnas-2121491119.pdf
Size:
1.73 MB
Format:
Adobe Portable Document Format
Download
Collections
Faculty Publications
BioSciences Publications
Chemistry Publications
Physics and Astronomy Publications