![[feed]](/style/images/feed-icon-14x14.png){kind=icon}
Tools
Tools
Preview |
PDF (Publisher's Version)
- Requires a PDF viewer such as GSview, Xpdf or Adobe Acrobat Reader
38MB |
![[thumbnail of Supplemental Information]](https://edoc.mdc-berlin.de/style/images/fileicons/other.png) |
Other (Supplemental Information)
502MB |
| Item Type: | Article |
|---|---|
| Title: | Cystine import and oxidative catabolism fuel vascular growth and repair via nutrient-responsive histone acetylation |
| Creators Name: | Drekolia, Maria-Kyriaki, Mettner, Janina, Wang, Daiyu, Delgado Lagos, Fredy, Koch, Christian, Hecker, Dennis, Eresch, Jeanette, Mao, Yifang, Bähr, Marion, Weichenhan, Dieter, Cordero, Julio, Wittig, Janina, Zhang, Boran, Cui, Hanyu, Li, Xiaoming, Oo, James A., Weigert, Andreas, Siragusa, Mauro, Klatt, Stephan, Fleming, Ingrid, Günther, Stefan, Looso, Mario, Brandes, Ralf P., Langer, Harald F., Papapetropoulos, Andreas, Singhal, Mahak, Schulz, Marcel H., Plass, Christoph, Heineke, Joerg, Dobreva, Gergana, Hu, Jiong and Bibli, Sofia-Iris |
| Abstract: | Endothelial metabolism underpins tissue regeneration, health, and longevity. We uncover a nuclear oxidative catabolic pathway linking cystine to gene regulation. Cells preparing to proliferate upregulate the SLC7A11 transporter to import cystine, which is oxidatively catabolized by cystathionine-γ-lyase (CSE) in the nucleus. This generates acetyl units via pyruvate dehydrogenase, driving site-specific histone H3 acetylation and chromatin remodeling that sustain endothelial transcription and proliferation. Combined loss of SLC7A11 and CSE abolishes cystine oxidative and reductive metabolism and causes embryonic lethality, whereas single deletions reveal distinct effects. SLC7A11 deficiency triggers compensatory cysteine de novo biosynthesis, partially maintaining angiogenesis, while CSE deletion disrupts nuclear cystine oxidative catabolism, transcription, and vessel formation. Therapeutically, cystine supplementation promotes vascular repair in retinopathy of prematurity, myocardial infarction, and injury in aging. These findings establish the role of cystine nuclear oxidative catabolism as a fundamental metabolic axis coupling nutrient utilization to gene regulation, with implications for vascular regeneration. |
| Source: | Cell Metabolism |
| ISSN: | 1550-4131 |
| Publisher: | Cell Press / Elsevier |
| Date: | 31 October 2025 |
| Additional Information: | ProteomeXchange dataset PXD068385 has been reserved by the PRIDE repository for a dataset that has been deposited, but is not yet publicly released and announced to ProteomeXchange. Accession "GSE305819", "GSE305820", "GSE305822", "GSE305823", "GSE305824", "GSE305826" and "GSE305827" are currently private and are scheduled to be released on Aug 18, 2026. |
| Official Publication: | https://doi.org/10.1016/j.cmet.2025.10.003 |
| PubMed: | View item in PubMed |
| Related to: |
Repository Staff Only: item control page
