Probing mitochondrial membrane potential

Abstract

Mitochondrial membrane potential, an indicator of mitochondrial function, is perturbed in many diseases , including cancer and neurodegenerative diseases, but difficult to measure noninvasively. Now, Elena A. Goun of the Swiss Federal Institute of Technology, Lausanne (EPFL) and coworkers have devised a bioluminescent probe for monitoring mitochondrial membrane potential ( 2020, DOI: ). The probe comprises two parts, a triphenylphosphine-caged luciferin and a separate azido-triphenylphosphine. Both components use their triphenylphosphonium groups to target mitochondria, where they react via Staudinger ligation, uncaging the luciferin in the process. The luciferin is acted on by the enzyme luciferase, which the researchers engineer into cells and mice. The enzymatic reaction releases light, the intensity of which is proportional to the concentration of the two parts of the probe. The rate enhancement of the reaction in the mitochondria relative to the rest of the cell enables measurement of the mitochondrial membrane potential. The researchers used