Skip to main content

Research Repository

Advanced Search

Cationic Europium Complexes for Visualizing Fluctuations in Mitochondrial ATP Levels in Living Cells

Mailhot, Romain; Traviss-Pollard, Thomas; Pal, Robert; Butler, Stephen Jonathan

Cationic Europium Complexes for Visualizing Fluctuations in Mitochondrial ATP Levels in Living Cells Thumbnail


Authors

Romain Mailhot

Thomas Traviss-Pollard

Stephen Jonathan Butler



Abstract

The ability to study cellular metabolism and enzymatic processes involving adenosine triphosphate (ATP) is impeded by the lack of imaging probes capable of signalling the concentration and distribution of intracellular ATP rapidly, with high sensitivity. We report here the first example of a luminescent lanthanide complex capable of visualizing changes in the concentration of ATP in the mitochondria of living cells. Four cationic europium(III) complexes [Eu.1–4]+ have been synthesized and their binding capabilities towards nucleoside polyphosphate anions examined in aqueous solution at physiological pH. Complexes [Eu.1]+ and [Eu.3]+ bearing hydrogen bond donor groups in the pendant arms showed excellent discrimination between ATP, ADP and monophosphate species. Complex [Eu.3]+ showed relatively strong binding to ATP (logKa=5.8), providing a rapid, long‐lived luminescent signal that enabled its detection in a highly competitive aqueous medium containing biologically relevant concentrations of Mg2+, ADP, GTP, UTP and human serum albumin. This EuIII complex responds linearly to ATP within the physiological concentration range (1–5 mm), and was used to continuously monitor the apyrase‐catalyzed hydrolysis of ATP to ADP in vitro. We demonstrate that [Eu.3]+ can permeate mammalian (NIH‐3T3) cells efficiently and localize to the mitochondria selectively, permitting real‐time visualization of elevated mitochondrial ATP levels following treatment with a broad spectrum kinase inhibitor, staurosporine, as well as depleted ATP levels upon treatment with potassium cyanide under glucose starvation conditions.

Citation

Mailhot, R., Traviss-Pollard, T., Pal, R., & Butler, S. J. (2018). Cationic Europium Complexes for Visualizing Fluctuations in Mitochondrial ATP Levels in Living Cells. Chemistry - A European Journal, 24(42), 10745-10755. https://doi.org/10.1002/chem.201801008

Journal Article Type Article
Acceptance Date May 10, 2018
Online Publication Date Jun 28, 2018
Publication Date Jul 25, 2018
Deposit Date May 30, 2018
Publicly Available Date Mar 29, 2024
Journal Chemistry - A European Journal
Print ISSN 0947-6539
Electronic ISSN 1521-3765
Publisher Wiley
Peer Reviewed Peer Reviewed
Volume 24
Issue 42
Pages 10745-10755
DOI https://doi.org/10.1002/chem.201801008

Files

Accepted Journal Article (1.6 Mb)
PDF

Copyright Statement
2018 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any
medium, provided the original work is properly cited.






You might also like



Downloadable Citations