Redox-dependent gating of VDAC by mitoNEET
dc.citation.firstpage | 19924 | en_US |
dc.citation.issueNumber | 40 | en_US |
dc.citation.journalTitle | Proceedings of the National Academy of Sciences | en_US |
dc.citation.lastpage | 19929 | en_US |
dc.citation.volumeNumber | 116 | en_US |
dc.contributor.author | Lipper, Colin H. | en_US |
dc.contributor.author | Stofleth, Jason T. | en_US |
dc.contributor.author | Bai, Fang | en_US |
dc.contributor.author | Sohn, Yang-Sung | en_US |
dc.contributor.author | Roy, Susmita | en_US |
dc.contributor.author | Mittler, Ron | en_US |
dc.contributor.author | Nechushtai, Rachel | en_US |
dc.contributor.author | Onuchic, José Nelson | en_US |
dc.contributor.author | Jennings, Patricia A. | en_US |
dc.date.accessioned | 2019-10-23T14:49:57Z | en_US |
dc.date.available | 2019-10-23T14:49:57Z | en_US |
dc.date.issued | 2019 | en_US |
dc.description.abstract | MitoNEET 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. | en_US |
dc.identifier.citation | Lipper, 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. | en_US |
dc.identifier.doi | https://doi.org/10.1073/pnas.1908271116 | en_US |
dc.identifier.uri | https://hdl.handle.net/1911/107489 | en_US |
dc.language.iso | eng | en_US |
dc.publisher | National Academy of Sciences | en_US |
dc.rights | This open access article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND). | en_US |
dc.rights.uri | https://creativecommons.org/licenses/by-nc-nd/4.0/ | en_US |
dc.title | Redox-dependent gating of VDAC by mitoNEET | en_US |
dc.type | Journal article | en_US |
dc.type.dcmi | Text | en_US |
dc.type.publication | publisher version | en_US |
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