title: Mitochondrial Nitroreductase Activity Enables Selective Imaging and Therapeutic Targeting.
abstract: Nitroreductase (NTR) activities have been known for decades, studied extensively in bacteria and also in systems as diverse as yeast, trypanosomes, and hypoxic tumors. The putative bacterial origin of mitochondria prompted us to explore the possible existence of NTR activity within this organelle and to probe its behavior in a cellular context. Presently, by using a profluorescent near-infrared (NIR) dye, we characterize the nature of NTR activity localized in mammalian cell mitochondria. Further, we demonstrate that this mitochondrially localized enzymatic activity can be exploited both for selective NIR imaging of mitochondria and for mitochondrial targeting by activating a mitochondrial poison specifically within that organelle. This constitutes a new mechanism for mitochondrial imaging and targeting. These findings represent the first use of mitochondrial enzyme activity to unmask agents for mitochondrial fluorescent imaging and therapy, which may prove to be more broadly applicable.
authors: Biodesign Center for BioEnergetics, and School of Molecular Sciences, Arizona State University , Tempe, Arizona 85287, United States.
authors: Arnaud
authors: A
authors: Chevalier
authors: Biodesign Center for BioEnergetics, and School of Molecular Sciences, Arizona State University , Tempe, Arizona 85287, United States.
authors: Yanmin
authors: Y
authors: Zhang
authors: Biodesign Center for BioEnergetics, and School of Molecular Sciences, Arizona State University , Tempe, Arizona 85287, United States.
authors: Omar M
authors: OM
authors: Khdour
authors: Biodesign Center for BioEnergetics, and School of Molecular Sciences, Arizona State University , Tempe, Arizona 85287, United States.
authors: Justin B
authors: JB
authors: Kaye
authors: Biodesign Center for BioEnergetics, and School of Molecular Sciences, Arizona State University , Tempe, Arizona 85287, United States.
authors: Sidney M
authors: SM
authors: Hecht
mesh_terms: D000072283:A549 Cells; D000968:Antimycin A / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology; D004926:Escherichia coli / Q000201:enzymology; D005456:Fluorescent Dyes / Q000737:chemistry; D006801:Humans; D008928:Mitochondria / Q000187:drug effects / Q000201:enzymology*; D015394:Molecular Structure; D009601:Nitroreductases / Q000235:genetics / Q000378:metabolism*; D061848:Optical Imaging; D019265:Spectroscopy, Near-Infrared
chemical_list: D005456:Fluorescent Dyes; D000968:Antimycin A; D009601:Nitroreductases