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Author Notes:

Correspondence: Y.-M. Go, Division of Pulmonary Medicine, Emory University, Atlanta, GA 30322; Fax: +1 404 712 2974; Email: ygo@emory.edu

and D.P. Jones, Division of Pulmonary Medicine, Emory University, Atlanta, GA 30322; Email: dpjones@emory.edu


Research Funding:

This work was supported by NIH Grants ES011195, ES009047, and HL083120.


  • Actin
  • Cytoskeleton
  • Endothelial cells
  • Extracellular redox state
  • Mitochondrial thioredoxin 2
  • Proinflammatory signaling
  • Redox proteomics
  • Redox ICAT
  • Free radicals

A key role for mitochondria in endothelial signaling by plasma cysteine/cystine redox potential

Journal Title:

Free Radical Biology and Medicine


Volume 48, Number 2


, Pages 275-283

Type of Work:

Article | Post-print: After Peer Review


The redox potential of the plasma cysteine/cystine couple (EhCySS) is oxidized in association with risk factors for cardiovascular disease (CVD), including age, smoking, type 2 diabetes, obesity, and alcohol abuse. Previous in vitro findings support a cause–effect relationship for extracellular EhCySS in cell signaling pathways associated with CVD, including those controlling monocyte adhesion to endothelial cells. In this study, we provide evidence that mitochondria are a major source of reactive oxygen species (ROS) in the signaling response to a more oxidized extracellular EhCySS. This increase in ROS was blocked by overexpression of mitochondrial thioredoxin-2 (Trx2) in endothelial cells from Trx2-transgenic mice, suggesting that mitochondrial thiol antioxidant status plays a key role in this redox signaling mechanism. Mass spectrometry-based redox proteomics showed that several classes of plasma membrane and cytoskeletal proteins involved in inflammation responded to this redox switch, including vascular cell adhesion molecule, integrins, actin, and several Ras family GTPases. Together, the data show that the proinflammatory effects of oxidized plasma EhCySS are due to a mitochondrial signaling pathway that is mediated through redox control of downstream effector proteins.

Copyright information:

© 2009 Elsevier Inc. All rights reserved.

This is an Open Access work distributed under the terms of the Creative Commons Attribution-NonCommerical-NoDerivs 3.0 Unported License (http://creativecommons.org/licenses/by-nc-nd/3.0/).

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