@article{Issitt:2019:10.1016/j.isci.2018.12.005,
author = {Issitt, T and Bosseboeuf, E and De, Winter N and Dufton, N and Gestri, G and Senatore, V and Chikh, A and Randi, AM and Raimondi, C},
doi = {10.1016/j.isci.2018.12.005},
journal = {iScience},
pages = {205--223},
title = {Neuropilin-1 controls endothelial homeostasis by regulating mitochondrial function and iron-dependent oxidative stress via ABCB8},
url = {http://dx.doi.org/10.1016/j.isci.2018.12.005},
volume = {11},
year = {2019}
}

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TY  - JOUR
AB  - The transmembrane protein Neuropilin-1 (NRP1) promotes vascular endothelial growth factor (VEGF) and extracellular matrix signalling in endothelial cells (ECs). Although it is established that NRP1 is essential for angiogenesis, little is known about its role in EC homeostasis. Here, we report that NRP1 promotes mitochondrial function in ECs by preventing iron accumulation and iron-induced oxidative stress through a VEGF-independent mechanism in non-angiogenic ECs. Furthermore, NRP1-deficient ECs have reduced growth and show the hallmarks of cellular senescence. We show that a subcellular pool of NRP1 localises in mitochondria and interacts with the mitochondrial transporter ATP-binding-cassette-B8 (ABCB8). NRP1 loss reduces ABCB8 levels, resulting in iron accumulation, iron-induced mitochondrial superoxide production and iron-dependent EC senescence. Treatment of NRP1-deficient ECs with the mitochondria-targeted antioxidant compound mitoTEMPO or with the iron chelator deferoxamine restores mitochondrial activity, inhibits superoxide production and protects from cellular senescence. This finding identifies an unexpected role of NRP1 in EC homeostasis.
AU  - Issitt,T
AU  - Bosseboeuf,E
AU  - De,Winter N
AU  - Dufton,N
AU  - Gestri,G
AU  - Senatore,V
AU  - Chikh,A
AU  - Randi,AM
AU  - Raimondi,C
DO  - 10.1016/j.isci.2018.12.005
EP  - 223
PY  - 2019///
SN  - 2589-0042
SP  - 205
TI  - Neuropilin-1 controls endothelial homeostasis by regulating mitochondrial function and iron-dependent oxidative stress via ABCB8
T2  - iScience
UR  - http://dx.doi.org/10.1016/j.isci.2018.12.005
UR  - http://hdl.handle.net/10044/1/65066
VL  - 11
ER  - 

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