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- Title
Mitochondrial ROS, uncoupled from ATP synthesis, determine endothelial activation for both physiological recruitment of patrolling cells and pathological recruitment of inflammatory cells<sup>1</sup>.
- Authors
Li, Xinyuan; Fang, Pu; Yang, William Y.; Chan, Kylie; Lavallee, Muriel; Xu, Keman; Gao, Tracy; Wang, Hong; Yang, Xiaofeng
- Abstract
Mitochondrial reactive oxygen species (mtROS) are signaling molecules, which drive inflammatory cytokine production and T cell activation. In addition, cardiovascular diseases, cancers, and autoimmune diseases all share a common feature of increased mtROS level. Both mtROS and ATP are produced as a result of electron transport chain activity, but it remains enigmatic whether mtROS could be generated independently from ATP synthesis. A recent study shed light on this important question and found that, during endothelial cell (EC) activation, mtROS could be upregulated in a proton leak-coupled, but ATP synthesis-uncoupled manner. As a result, EC could upregulate mtROS production for physiological EC activation without compromising mitochondrial membrane potential and ATP generation, and consequently without causing mitochondrial damage and EC death. Thus, a novel pathophysiological role of proton leak in driving mtROS production was uncovered for low grade EC activation, patrolling immunosurveillance cell trans-endothelial migration and other signaling events without compromising cellular survival. This new working model explains how mtROS could be increasingly generated independently from ATP synthesis and endothelial damage or death. Mapping the connections among mitochondrial metabolism, physiological EC activation, patrolling cell migration, and pathological inflammation is significant towards the development of novel therapies for inflammatory diseases and cancers.
- Subjects
MITOCHONDRIA; ACTIVE oxygen in the body; CARDIOVASCULAR diseases risk factors; ELECTRON transport; ENDOTHELIAL cells; MITOCHONDRIAL membranes; ADENOSINE triphosphate; CHEMICAL synthesis
- Publication
Canadian Journal of Physiology & Pharmacology, 2017, Vol 95, Issue 3, p247
- ISSN
0008-4212
- Publication type
Article
- DOI
10.1139/cjpp-2016-0515