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Prohibitin-1 maintains the angiogenic capacity of endothelial cells by regulating mitochondrial function and senescence

Prohibitin-1 maintains the angiogenic capacity of endothelial cells by regulating mitochondrial... Prohibitin 1 (PHB1) is a highly conserved protein that is mainly localized to the inner mitochondrial membrane and has been implicated in regulating mitochondrial function in yeast. Because mitochondria are emerging as an important regulator of vascular homeostasis, we examined PHB1 function in endothelial cells. PHB1 is highly expressed in the vascular system and knockdown of PHB1 in endothelial cells increases mitochondrial production of reactive oxygen species via inhibition of complex I, which results in cellular senescence. As a direct consequence, both Akt and Rac1 are hyperactivated, leading to cytoskeletal rearrangements and decreased endothelial cell motility, e.g., migration and tube formation. This is also reflected in an in vivo angiogenesis assay, where silencing of PHB1 blocks the formation of functional blood vessels. Collectively, our results provide evidence that PHB1 is important for mitochondrial function and prevents reactive oxygen species–induced senescence and thereby maintains the angiogenic capacity of endothelial cells. Footnotes Abbreviations used in this paper: BAEC, bovine aortic endothelial cell; EC, endothelial cell; HUVEC, human umbilical vein EC; PAK, p21-activated kinase; PECAM-1, platelet EC adhesion molecule 1; PEG, polyethylene glycol; PHB1, prohibitin-1; PI3-K, phosphatidyl inositol 3-kinase; ROS, reactive oxygen species; SMC, smooth muscle cell. Submitted: 11 June 2007 Accepted: 10 December 2007 http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png The Journal of Cell Biology Rockefeller University Press

Prohibitin-1 maintains the angiogenic capacity of endothelial cells by regulating mitochondrial function and senescence

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References (55)

Publisher
Rockefeller University Press
Copyright
Copyright © 2008, by The Rockefeller University Press
ISSN
0021-9525
eISSN
1540-8140
DOI
10.1083/jcb.200706072
pmid
18195103
Publisher site
See Article on Publisher Site

Abstract

Prohibitin 1 (PHB1) is a highly conserved protein that is mainly localized to the inner mitochondrial membrane and has been implicated in regulating mitochondrial function in yeast. Because mitochondria are emerging as an important regulator of vascular homeostasis, we examined PHB1 function in endothelial cells. PHB1 is highly expressed in the vascular system and knockdown of PHB1 in endothelial cells increases mitochondrial production of reactive oxygen species via inhibition of complex I, which results in cellular senescence. As a direct consequence, both Akt and Rac1 are hyperactivated, leading to cytoskeletal rearrangements and decreased endothelial cell motility, e.g., migration and tube formation. This is also reflected in an in vivo angiogenesis assay, where silencing of PHB1 blocks the formation of functional blood vessels. Collectively, our results provide evidence that PHB1 is important for mitochondrial function and prevents reactive oxygen species–induced senescence and thereby maintains the angiogenic capacity of endothelial cells. Footnotes Abbreviations used in this paper: BAEC, bovine aortic endothelial cell; EC, endothelial cell; HUVEC, human umbilical vein EC; PAK, p21-activated kinase; PECAM-1, platelet EC adhesion molecule 1; PEG, polyethylene glycol; PHB1, prohibitin-1; PI3-K, phosphatidyl inositol 3-kinase; ROS, reactive oxygen species; SMC, smooth muscle cell. Submitted: 11 June 2007 Accepted: 10 December 2007

Journal

The Journal of Cell BiologyRockefeller University Press

Published: Jan 14, 2008

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