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@ARTICLE{Drekolia:305605,
author = {M.-K. Drekolia and J. Mettner and D. Wang and F. Delgado
Lagos and C. Koch and D. Hecker and J. Eresch and Y. Mao and
M. Bähr$^*$ and D. Weichenhan$^*$ and J. Cordero and J.
Wittig and B. Zhang and H. Cui and X. Li and J. A. Oo and A.
Weigert and M. Siragusa and S. Klatt and I. Fleming and S.
Günther and M. Looso and R. P. Brandes and H. F. Langer and
A. Papapetropoulos and M. Singhal and M. H. Schulz and C.
Plass$^*$ and J. Heineke and G. Dobreva and J. Hu and S.-I.
Bibli},
title = {{C}ystine import and oxidative catabolism fuel vascular
growth and repair via nutrient-responsive histone
acetylation.},
journal = {Cell metabolism},
volume = {nn},
issn = {1550-4131},
address = {Amsterdam [u.a.]},
publisher = {Elsevier},
reportid = {DKFZ-2025-02255},
pages = {nn},
year = {2025},
note = {epub},
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.},
keywords = {CSE (Other) / SLC7A11 (Other) / aging (Other) / cystine
(Other) / epigenetics (Other) / vascular growth (Other)},
cin = {B370},
ddc = {570},
cid = {I:(DE-He78)B370-20160331},
pnm = {312 - Funktionelle und strukturelle Genomforschung
(POF4-312)},
pid = {G:(DE-HGF)POF4-312},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:41175867},
doi = {10.1016/j.cmet.2025.10.003},
url = {https://inrepo02.dkfz.de/record/305605},
}