A Bioluminescent Probe for Longitudinal Monitoring of Mitochondrial Membrane Potential

Overview

Journal Nat Chem Biol

Specialties Biochemistry
Biology
Chemistry

Date 2020 Aug 12

PMID 32778841

Citations 10

Authors

Arkadiy A Bazhin

Riccardo Sinisi

Umberto De Marchi

Aurelie Hermant

Nicolas Sambiagio

Tamara Maric

Ghyslain Budin

Elena A Goun

Affiliations

Soon will be listed here.

Abstract

Mitochondrial membrane potential (ΔΨ) is a universal selective indicator of mitochondrial function and is known to play a central role in many human pathologies, such as diabetes mellitus, cancer and Alzheimer's and Parkinson's diseases. Here, we report the design, synthesis and several applications of mitochondria-activatable luciferin (MAL), a bioluminescent probe sensitive to ΔΨ, and partially to plasma membrane potential (ΔΨ), for non-invasive, longitudinal monitoring of ΔΨ in vitro and in vivo. We applied this new technology to evaluate the aging-related change of ΔΨ in mice and showed that nicotinamide riboside (NR) reverts aging-related mitochondrial depolarization, revealing another important aspect of the mechanism of action of this potent biomolecule. In addition, we demonstrated application of the MAL probe for studies of brown adipose tissue (BAT) activation and non-invasive in vivo assessment of ΔΨ in animal cancer models, opening exciting opportunities for understanding the underlying mechanisms and for discovery of effective treatments for many human pathologies.

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