title: Genetically encoded redox sensors.
abstract: Endogenous redox sensors detect fluctuations in the intracellular redox equilibrium and are critical for the maintenance of homeostasis. Such systems have been exploited to engineer genetically encoded redox sensors to detect dynamic oxidative changes within a cellular environment. Most genetically encoded redox sensors detect reactive oxygen species (ROS) such as superoxide anion, hydrogen peroxide and hydroxyl radical. Technical hurdles including the limited temporal and spatial resolution as well as tissue heterogeneity have complicated the realization of the full potential of genetically encoded redox sensors in animals until recently. Alterations in the concentration and subcellular localization of ROS are integral to numerous disorders, including neurodegenerative diseases and cancer. Thus, genetically encoded redox sensors are useful for the study of the pathogenesis and progression of multiple diseases. Moreover, the ultimate generation of genetically encoded redox sensors provides substantial advantages over conventional methods such as ROS-sensitive fluorescent probes. Here, we review examples of genetically encoded redox sensors, present their application to various fields of biomedical investigation, including the study of oncometabolism, discuss their drawbacks and explore future developments.
authors.affiliation: Department of Pharmacology & Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA; Pittsburgh Institute for Neurodegenerative Diseases, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
authors.forename: Wai Kan
authors.initials: WK
authors.lastname: Chiu
authors.affiliation: Department of Pharmacology & Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA; Pittsburgh Institute for Neurodegenerative Diseases, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
authors.forename: Atif
authors.initials: A
authors.lastname: Towheed
authors.affiliation: Department of Pharmacology & Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA; Pittsburgh Institute for Neurodegenerative Diseases, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA. Electronic address: mjp44@pitt.edu.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Palladino
mesh_terms: D001671:Biochemistry / Q000379:methods*; D015374:Biosensing Techniques / Q000379:methods*; D005818:Genetic Engineering / Q000379:methods*; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D009369:Neoplasms / Q000378:metabolism; D009569:Nitric Oxide / Q000032:analysis; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D017382:Reactive Oxygen Species; D013312:Stress, Physiological; D013481:Superoxides / Q000378:metabolism
chemical_list: D017382:Reactive Oxygen Species; D013481:Superoxides; D049452:Green Fluorescent Proteins; D009569:Nitric Oxide
keywords: Hydrogen peroxide; Hydroxyl radical; Mitochondria; Reactive oxygen species; Respiratory chain; Superoxide anion