Dataset Information

Neuropilin-1 Controls Endothelial Homeostasis by Regulating Mitochondrial Function and Iron-Dependent Oxidative Stress.

ABSTRACT: The transmembrane protein neuropilin-1 (NRP1) promotes vascular endothelial growth factor (VEGF) and extracellular matrix signaling 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 localizes 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.

SUBMITTER: Issitt T

PROVIDER: S-EPMC6327076 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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Neuropilin-1 Controls Endothelial Homeostasis by Regulating Mitochondrial Function and Iron-Dependent Oxidative Stress.

Issitt Theo T Bosseboeuf Emy E De Winter Natasha N Dufton Neil N Gestri Gaia G Senatore Valentina V Chikh Anissa A Randi Anna M AM Raimondi Claudio C

iScience 20181211

The transmembrane protein neuropilin-1 (NRP1) promotes vascular endothelial growth factor (VEGF) and extracellular matrix signaling 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 ...[more]

PMID: 30623799

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Dataset Information

Neuropilin-1 Controls Endothelial Homeostasis by Regulating Mitochondrial Function and Iron-Dependent Oxidative Stress.

Publications

Neuropilin-1 Controls Endothelial Homeostasis by Regulating Mitochondrial Function and Iron-Dependent Oxidative Stress.

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