title: Mitochondrial signaling in the vascular endothelium: beyond reactive oxygen species.
abstract: Traditionally, the mitochondria have been viewed as the cell's powerhouse, producing energy in the form of ATP. As a byproduct of ATP formation, the mitochondrial electron transport chain produces substantial amounts of reactive oxygen species (ROS). First thought to be toxic, recent literature indicates an important signaling function for mitochondria-derived ROS, especially in relation to cardiovascular disease pathogenesis. This has spawned an evolution to a more contemporary view of mitochondrial function as a dynamic organelle involved in key regulatory and cell survival processes. Beyond ROS, recent studies have identified a host of mitochondria-linked factors that influence the cellular and extracellular environments, including mitochondria-derived peptides, mitochondria-localized proteins, and the mitochondrial genome itself. Interestingly, many of these factors help orchestrate ROS homeostasis and ROS-related signaling. The paradigm defining the role of mitochondria in the vasculature needs to be updated yet again to include these key signaling factors, which serves as the focus of the current review. In describing these novel signaling factors, we pay specific attention to their influence on endothelial homeostasis. Therapies targeting these pathways are discussed, as are emerging research directions.
authors.affiliation: Department of Physiology, Medical College of Wisconsin, Milwaukee, WI, USA.|Cardiovascular Center, Medical College of Wisconsin, Milwaukee, WI, USA.
authors.forename: Andrew O
authors.initials: AO
authors.lastname: Kadlec
authors.affiliation: Department of Physiology, Medical College of Wisconsin, Milwaukee, WI, USA.|Division of Cardiology, Cardiovascular Center, Department of Medicine, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI, 53226, USA.|Cardiovascular Center, Medical College of Wisconsin, Milwaukee, WI, USA.
authors.forename: Andreas M
authors.initials: AM
authors.lastname: Beyer
authors.affiliation: Department of Physiology, Medical College of Wisconsin, Milwaukee, WI, USA.|Division of Cardiology, Cardiovascular Center, Department of Medicine, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI, 53226, USA.|Cardiovascular Center, Medical College of Wisconsin, Milwaukee, WI, USA.
authors.forename: Karima
authors.initials: K
authors.lastname: Ait-Aissa
authors.affiliation: Department of Physiology, Medical College of Wisconsin, Milwaukee, WI, USA. dgutt@mcw.edu.|Division of Cardiology, Cardiovascular Center, Department of Medicine, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI, 53226, USA. dgutt@mcw.edu.|Cardiovascular Center, Medical College of Wisconsin, Milwaukee, WI, USA. dgutt@mcw.edu.|Department of Veterans Administration Medical Center, Milwaukee, WI, USA. dgutt@mcw.edu.
authors.forename: David D
authors.initials: DD
authors.lastname: Gutterman
mesh_terms: D000818:Animals; D004730:Endothelium, Vascular / Q000378:metabolism*; D006801:Humans; D008928:Mitochondria / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D017382:Reactive Oxygen Species
keywords: Cardiovascular disease; Endothelium; Mitochondria; Reactive oxygen species