Mitochondrial Nitroreductase Activity Enables Selective Imaging and Therapeutic Targeting

Arnaud Chevalier, Yanmin Zhang, Omar Khdour, Justin B. Kaye, Sidney Hecht

Research output: Contribution to journalArticle

61 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)12009-12012
Number of pages4
JournalJournal of the American Chemical Society
Volume138
Issue number37
DOIs
StatePublished - Sep 21 2016

Fingerprint

Nitroreductases
Mitochondria
Imaging techniques
Organelles
Trypanosomiasis
Poisons
Infrared imaging
Enzyme activity
Fluorescent Dyes
Yeast
Tumors
Bacteria
Coloring Agents
Therapeutics
Dyes
Yeasts
Cells
Infrared radiation
Enzymes
Neoplasms

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry

Cite this

Mitochondrial Nitroreductase Activity Enables Selective Imaging and Therapeutic Targeting. / Chevalier, Arnaud; Zhang, Yanmin; Khdour, Omar; Kaye, Justin B.; Hecht, Sidney.

In: Journal of the American Chemical Society, Vol. 138, No. 37, 21.09.2016, p. 12009-12012.

Research output: Contribution to journalArticle

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