TY - JOUR
T1 - Mitochondrial Nitroreductase Activity Enables Selective Imaging and Therapeutic Targeting
AU - Chevalier, Arnaud
AU - Zhang, Yanmin
AU - Khdour, Omar
AU - Kaye, Justin B.
AU - Hecht, Sidney
N1 - Publisher Copyright:
© 2016 American Chemical Society.
PY - 2016/9/21
Y1 - 2016/9/21
N2 - 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.
AB - 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.
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U2 - 10.1021/jacs.6b06229
DO - 10.1021/jacs.6b06229
M3 - Article
C2 - 27571326
AN - SCOPUS:84988598824
SN - 0002-7863
VL - 138
SP - 12009
EP - 12012
JO - Journal of the American Chemical Society
JF - Journal of the American Chemical Society
IS - 37
ER -