title: Mitochondrial ROS, uncoupled from ATP synthesis, determine endothelial activation for both physiological recruitment of patrolling cells and pathological recruitment of inflammatory cells.
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.
authors.affiliation: Centers for Metabolic Disease Research, Cardiovascular Research, and Thrombosis Research, Department of Pharmacology, Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, USA.|Centers for Metabolic Disease Research, Cardiovascular Research, and Thrombosis Research, Department of Pharmacology, Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, USA.
authors.forename: Xinyuan
authors.initials: X
authors.lastname: Li
authors.affiliation: Centers for Metabolic Disease Research, Cardiovascular Research, and Thrombosis Research, Department of Pharmacology, Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, USA.|Centers for Metabolic Disease Research, Cardiovascular Research, and Thrombosis Research, Department of Pharmacology, Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, USA.
authors.forename: Pu
authors.initials: P
authors.lastname: Fang
authors.affiliation: Centers for Metabolic Disease Research, Cardiovascular Research, and Thrombosis Research, Department of Pharmacology, Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, USA.|Centers for Metabolic Disease Research, Cardiovascular Research, and Thrombosis Research, Department of Pharmacology, Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, USA.
authors.forename: William Y
authors.initials: WY
authors.lastname: Yang
authors.affiliation: Centers for Metabolic Disease Research, Cardiovascular Research, and Thrombosis Research, Department of Pharmacology, Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, USA.|Centers for Metabolic Disease Research, Cardiovascular Research, and Thrombosis Research, Department of Pharmacology, Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, USA.
authors.forename: Kylie
authors.initials: K
authors.lastname: Chan
authors.affiliation: Centers for Metabolic Disease Research, Cardiovascular Research, and Thrombosis Research, Department of Pharmacology, Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, USA.|Centers for Metabolic Disease Research, Cardiovascular Research, and Thrombosis Research, Department of Pharmacology, Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, USA.
authors.forename: Muriel
authors.initials: M
authors.lastname: Lavallee
authors.affiliation: Centers for Metabolic Disease Research, Cardiovascular Research, and Thrombosis Research, Department of Pharmacology, Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, USA.|Centers for Metabolic Disease Research, Cardiovascular Research, and Thrombosis Research, Department of Pharmacology, Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, USA.
authors.forename: Keman
authors.initials: K
authors.lastname: Xu
authors.affiliation: Centers for Metabolic Disease Research, Cardiovascular Research, and Thrombosis Research, Department of Pharmacology, Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, USA.|Centers for Metabolic Disease Research, Cardiovascular Research, and Thrombosis Research, Department of Pharmacology, Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, USA.
authors.forename: Tracy
authors.initials: T
authors.lastname: Gao
authors.affiliation: Centers for Metabolic Disease Research, Cardiovascular Research, and Thrombosis Research, Department of Pharmacology, Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, USA.|Centers for Metabolic Disease Research, Cardiovascular Research, and Thrombosis Research, Department of Pharmacology, Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, USA.
authors.forename: Hong
authors.initials: H
authors.lastname: Wang
authors.affiliation: Centers for Metabolic Disease Research, Cardiovascular Research, and Thrombosis Research, Department of Pharmacology, Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, USA.|Centers for Metabolic Disease Research, Cardiovascular Research, and Thrombosis Research, Department of Pharmacology, Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, USA.
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Yang
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D002318:Cardiovascular Diseases / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D004734:Energy Metabolism; D006801:Humans; D007249:Inflammation / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D018836:Inflammation Mediators / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial; D008928:Mitochondria / Q000378:metabolism* / Q000473:pathology; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism*; D057705:Transendothelial and Transepithelial Migration
chemical_list: D018836:Inflammation Mediators; D017382:Reactive Oxygen Species; D000255:Adenosine Triphosphate
keywords: ROS; cancer; cardiovascular disease; dérivés réactifs de l’oxygène; inflammation vasculaire; maladies cardiovasculaires; mitochondria; mitochondrie; vascular inflammation