Activity-based ratiometric FRET probe reveals oncogene-driven changes in labile copper pools induced by altered glutathione metabolism
Article 2019 en
Authors
CC
Clive Yik‐Sham Chung
JP
Jessica M. Posimo
SL
Sumin Lee
Abstract
1 min read
Significance Copper is a required metal nutrient for life, yet its altered homeostasis is associated with many diseases. Thus, to develop new methods to help decipher copper biology, we present an activity-based ratiometric fluorescence resonance energy transfer (FRET) probe that exploits a biomimetic, copper(I)-dependent cleavage reaction to enable imaging of loosely bound, labile copper pools in cells with metal and oxidation state selectivity and a self-calibrating ratiometric response. Application of this technology to cellular models of cancer reveals that oncogene-driven changes in the metabolism of glutathione, a major cellular redox buffer, leads to a labile copper(I) deficiency. This work establishes the relevance of copper dysregulation to cancer metabolism and presages further opportunities for activity-based sensing in studies of metal biology.
Aidan T. Pezacki, Carson D. Matier, Xingxing Gu, Eric Kummelstedt, Sarah Bond, Laura Torrente, Kelly L. Jordan‐Sciutto, Gina M. DeNicola, Timothy A. Su, Donita C. Brady, Christopher J Chang
Marco S. Messina, Laura Torrente, Aidan T. Pezacki, Hanna I. Humpel, Erin L. Li, Sophia G. Miller, Odette Verdejo‐Torres, Teresita Padilla‐Benavides, Donita C. Brady, David W. Killilea, Alison N. Killilea, Martina Ralle, Nathan P. Ward, Jun Ohata, Gina M. DeNicola, Christopher J Chang
Discussion(0)
No comments yet. Be the first to comment.