TY  - JOUR
AU  - Drekolia, Maria-Kyriaki
AU  - Mettner, Janina
AU  - Wang, Daiyu
AU  - Delgado Lagos, Fredy
AU  - Koch, Christian
AU  - Hecker, Dennis
AU  - Eresch, Jeanette
AU  - Mao, Yifang
AU  - Bähr, Marion
AU  - Weichenhan, Dieter
AU  - Cordero, Julio
AU  - Wittig, Janina
AU  - Zhang, Boran
AU  - Cui, Hanyu
AU  - Li, Xiaoming
AU  - Oo, James A
AU  - Weigert, Andreas
AU  - Siragusa, Mauro
AU  - Klatt, Stephan
AU  - Fleming, Ingrid
AU  - Günther, Stefan
AU  - Looso, Mario
AU  - Brandes, Ralf P
AU  - Langer, Harald F
AU  - Papapetropoulos, Andreas
AU  - Singhal, Mahak
AU  - Schulz, Marcel H
AU  - Plass, Christoph
AU  - Heineke, Joerg
AU  - Dobreva, Gergana
AU  - Hu, Jiong
AU  - Bibli, Sofia-Iris
TI  - Cystine import and oxidative catabolism fuel vascular growth and repair via nutrient-responsive histone acetylation.
JO  - Cell metabolism
VL  - 38
IS  - 1
SN  - 1550-4131
CY  - Amsterdam [u.a.]
PB  - Elsevier
M1  - DKFZ-2025-02255
SP  - 115-134.e20
PY  - 2026
N1  - Volume 38, Issue 1, 6 January 2026, Pages 115-134.e20
AB  - 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.
KW  - CSE (Other)
KW  - SLC7A11 (Other)
KW  - aging (Other)
KW  - cystine (Other)
KW  - epigenetics (Other)
KW  - vascular growth (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:41175867
DO  - DOI:10.1016/j.cmet.2025.10.003
UR  - https://inrepo02.dkfz.de/record/305605
ER  -