Academic Journal
Iron drives anabolic metabolism through active histone demethylation and mTORC1
| العنوان: | Iron drives anabolic metabolism through active histone demethylation and mTORC1 |
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| المؤلفون: | Shapiro, Jason S., Chang, Hsiang Chun, Tatekoshi, Yuki, Zhao, Zibo, Waxali, Zohra Sattar, Hong, Bong Jin, Chen, Haimei, Geier, Justin A., Bartom, Elizabeth T., De Jesus, Adam, Nejad, Farnaz K., Mahmoodzadeh, Amir, Sato, Tatsuya, Ramos-Alonso, Lucia, Romero, Antonia Maria, Martinez-Pastor, Maria Teresa, Jiang, Shang Chuan, Sah-Teli, Shiv K., Li, Liming, Bentrem, David, Lopaschuk, Gary, Ben-Sahra, Issam, O’Halloran, Thomas V., Shilatifard, Ali, Puig, Sergi, Bergelson, Joy, Koivunen, Peppi, Ardehali, Hossein |
| المساهمون: | Ministerio de Ciencia, Innovación y Universidades (España), European Commission, Waxali, Zohra Sattar, Geier, Justin A., Bartom, Elizabeth T., De Jesus, Adam, Sato, Tatsuya, Martinez-Pastor, Maria Teresa, Jiang, Shang Chuan, Sah-Teli, Shiv K., Ben-Sahra, Issam, Shilatifard, Ali, Puig, Sergi, Ardehali, Hossein |
| بيانات النشر: | Springer Nature |
| سنة النشر: | 2023 |
| المجموعة: | Digital.CSIC (Consejo Superior de Investigaciones Científicas / Spanish National Research Council) |
| مصطلحات موضوعية: | iron, metabolism, histones |
| الوصف: | All eukaryotic cells require a minimal iron threshold to sustain anabolic metabolism. However, the mechanisms by which cells sense iron to regulate anabolic processes are unclear. Here we report a previously undescribed eukaryotic pathway for iron sensing in which molecular iron is required to sustain active histone demethylation and maintain the expression of critical components of the pro-anabolic mTORC1 pathway. Specifically, we identify the iron-binding histone-demethylase KDM3B as an intrinsic iron sensor that regulates mTORC1 activity by demethylating H3K9me2 at enhancers of a high-affinity leucine transporter, LAT3, and RPTOR. By directly suppressing leucine availability and RAPTOR levels, iron deficiency supersedes other nutrient inputs into mTORC1. This process occurs in vivo and is not an indirect effect by canonical iron-utilizing pathways. Because ancestral eukaryotes share homologues of KDMs and mTORC1 core components, this pathway probably pre-dated the emergence of the other kingdom-specific nutrient sensors for mTORC1. ; Metal analysis was performed at the Northwestern University Quantitative Bio-element Imaging Center generously supported by the National Research Resource for Quantitative Mapping in the Life Sciences (QE-Map) award number P41GM135018. Metabolomics services were performed by the Metabolomics Core Facility at Robert H. Lurie Comprehensive Cancer Center of Northwestern University. Proteomics services were performed by Y. Ah Goo, in conjunction with N. L. Kelleher at the Northwestern Proteomics Core Facility, generously supported by NCI CCSG P30 CA060553 awarded to the Robert H. Lurie Comprehensive Cancer Center, instrumentation award (S10OD025194) from NIH Office of Director, and the National Resource for Translational and Developmental Proteomics supported by P41 GM108569. We thank M. J. Schipma, and B. Wray at the Northwestern University Sequencing Core and P. A. Ozark for their contribution to the ChIP–seq analyses. This work was supported through core services and support from ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 1465-7392 |
| Relation: | #PLACEHOLDER_PARENT_METADATA_VALUE#; info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/BIO2017-87828-C2-1-P/ES/REGULACION TRANSCRIPCIONAL Y POSTRANSCRIPCIONAL DE PROCESOS METABOLICOS DEPENDIENTES DE LA DISPONIBILIDAD DE HIERRO Y COBRE EN LEVADURAS Y PLANTAS/; Nature Cell Biology; Preprint; https://doi.org/10.1038/s41556-023-01225-6; Sí; Nature Cell Biology 25(10):1478-1494 (2023); http://hdl.handle.net/10261/360915; 2-s2.0-85172133336; https://api.elsevier.com/content/abstract/scopus_id/85172133336 |
| DOI: | 10.21203/rs.3.rs-2042947/v1 |
| الاتاحة: | http://hdl.handle.net/10261/360915 https://doi.org/10.21203/rs.3.rs-2042947/v1 https://api.elsevier.com/content/abstract/scopus_id/85172133336 |
| Rights: | open |
| رقم الانضمام: | edsbas.BC0CC591 |
| قاعدة البيانات: | BASE |
| تدمد: | 14657392 |
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| DOI: | 10.21203/rs.3.rs-2042947/v1 |