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Cationic Europium complexes for visualizing fluctuations in Mitochondrial ATP levels in living cells

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journal contribution
posted on 01.10.2018, 10:00 authored by Romain Mailhot, Thomas Traviss-Pollard, Robert Pal, Stephen ButlerStephen Butler
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.

Funding

This work was supported by a Wellcome Trust Seed Award (204500/Z/16/Z) and a Royal Society of Chemistry Research Grant.

History

School

  • Science

Department

  • Chemistry

Published in

Chemistry

Citation

MAILHOT, R. ... et al., 2018. Cationic Europium complexes for visualizing fluctuations in Mitochondrial ATP levels in living cells. Chemistry - A European Journal, 24(42), pp. 10745-10755.

Publisher

© The Authors. Published by Wiley

Version

VoR (Version of Record)

Publisher statement

This work is made available according to the conditions of the Creative Commons Attribution 4.0 International (CC BY 4.0) licence. Full details of this licence are available at: http://creativecommons.org/licenses/ by/4.0/

Acceptance date

15/05/2018

Publication date

2018

Notes

This is an Open Access Article. It is published by Wiley under the Creative Commons Attribution 4.0 Unported Licence (CC BY). Full details of this licence are available at: http://creativecommons.org/licenses/by/4.0/

ISSN

0947-6539

eISSN

1521-3765

Language

en

Location

Germany