A bioluminescent probe for longitudinal monitoring of mitochondrial membrane potential.
Arkadiy A BazhinRiccardo SinisiUmberto De MarchiAurélie HermantNicolas SambiagioTamara MaricGhyslain BudinElena A GounPublished in: Nature chemical biology (2020)
Mitochondrial membrane potential (ΔΨm) 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 ΔΨm, and partially to plasma membrane potential (ΔΨp), for non-invasive, longitudinal monitoring of ΔΨm in vitro and in vivo. We applied this new technology to evaluate the aging-related change of ΔΨm 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 ΔΨm in animal cancer models, opening exciting opportunities for understanding the underlying mechanisms and for discovery of effective treatments for many human pathologies.
Keyphrases
- endothelial cells
- adipose tissue
- oxidative stress
- papillary thyroid
- living cells
- quantum dots
- squamous cell
- human health
- pluripotent stem cells
- squamous cell carcinoma
- induced pluripotent stem cells
- small molecule
- high throughput
- cross sectional
- fluorescent probe
- high fat diet
- cell death
- insulin resistance
- cognitive decline
- fluorescence imaging
- climate change
- weight loss
- high fat diet induced
- anti inflammatory
- reactive oxygen species
- single cell