Redox-dependent gating of VDAC by mitoNEET

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dc.citation.firstpage19924
dc.citation.issueNumber40
dc.citation.journalTitleProceedings of the National Academy of Sciences
dc.citation.lastpage19929
dc.citation.volumeNumber116
dc.contributor.authorLipper, Colin H.
dc.contributor.authorStofleth, Jason T.
dc.contributor.authorBai, Fang
dc.contributor.authorSohn, Yang-Sung
dc.contributor.authorRoy, Susmita
dc.contributor.authorMittler, Ron
dc.contributor.authorNechushtai, Rachel
dc.contributor.authorOnuchic, José Nelson
dc.contributor.authorJennings, Patricia A.
dc.date.accessioned2019-10-23T14:49:57Z
dc.date.available2019-10-23T14:49:57Z
dc.date.issued2019
dc.description.abstractMitoNEET is an outer mitochondrial membrane protein essential for sensing and regulation of iron and reactive oxygen species (ROS) homeostasis. It is a key player in multiple human maladies including diabetes, cancer, neurodegeneration, and Parkinson’s diseases. In healthy cells, mitoNEET receives its clusters from the mitochondrion and transfers them to acceptor proteins in a process that could be altered by drugs or during illness. Here, we report that mitoNEET regulates the outer-mitochondrial membrane (OMM) protein voltage-dependent anion channel 1 (VDAC1). VDAC1 is a crucial player in the cross talk between the mitochondria and the cytosol. VDAC proteins function to regulate metabolites, ions, ROS, and fatty acid transport, as well as function as a “governator” sentry for the transport of metabolites and ions between the cytosol and the mitochondria. We find that the redox-sensitive [2Fe-2S] cluster protein mitoNEET gates VDAC1 when mitoNEET is oxidized. Addition of the VDAC inhibitor 4,4′-diisothiocyanatostilbene-2,2′-disulfonate (DIDS) prevents both mitoNEET binding in vitro and mitoNEET-dependent mitochondrial iron accumulation in situ. We find that the DIDS inhibitor does not alter the redox state of MitoNEET. Taken together, our data indicate that mitoNEET regulates VDAC in a redox-dependent manner in cells, closing the pore and likely disrupting VDAC’s flow of metabolites.
dc.identifier.citationLipper, Colin H., Stofleth, Jason T., Bai, Fang, et al.. "Redox-dependent gating of VDAC by mitoNEET." <i>Proceedings of the National Academy of Sciences,</i> 116, no. 40 (2019) National Academy of Sciences: 19924-19929. https://doi.org/10.1073/pnas.1908271116.
dc.identifier.doihttps://doi.org/10.1073/pnas.1908271116
dc.identifier.urihttps://hdl.handle.net/1911/107489
dc.language.isoeng
dc.publisherNational Academy of Sciences
dc.rightsThis open access article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND).
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/
dc.titleRedox-dependent gating of VDAC by mitoNEET
dc.typeJournal article
dc.type.dcmiText
dc.type.publicationpublisher version
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