Membrane potential is the voltage difference between the inside and outside of a cell that powers the various molecules embedded in the membrane, which contain mitochondria membrane, myocardial membrane, neurons and so on. Especially, Mitochondria as the main energy supply structure of organisms, its electrical potential is an important physiological parameter employed to monitor health states of cells. Recently, classical fluorescent dyes, which contain TMRM (tetramethyl rhodamine methyl ester), TMRE (tetramethyl rhodamine ethyl ester), Rhodamine 123 (Rh 123), and JC-1 cationic groups, have been developed to synthesize membrane potential probes.
Fig.1 Structure of neurons, heart and mitochondria
Recent advances in mitochondrial membrane potential probes
Due to the special status of mitochondria, mitochondrial membrane potential detection technology has attracted extensive attention and research. The following is a brief introduction of the latest research progress of mitochondrial membrane potential probes, in order to provide reference for researchers.
- Jun Li and his co-workers designed and synthesized a novel mitochondrial membrane potential probes, which based on the combination of aggregation-induced emission (AIE) dyes and triphenylphosphonium (TPP) groups. The results of this effort show that in comparison to the first generation AIE luminogen developed for mitochondria tracking, the new probe, in which the TPP group is conjugated to the AIE through a double bond, has a longer emission wavelength enabling avoidance of autofluor-escence in the cell. Furthermore, the probe is stable in the present of both biothiols and ROS, and it is sensitive to membrane potential change.
Fig.2 Structures of TPP-based probe 1 and 2.
- Arkadiy  and his co-workers have developed a novel mitochondria-activatable luciferin (MAL) probe that allows us to monitor changes in mitochondrial membrane potential (ΔΨm) in a non-invasive, longitudinal fashion both in vitro and in vivo. The approach is based on the combination of a mitochondria-targeted biorthogonal click reaction and a sensitive bioluminescent imaging (BLI) technique, which is the most sensitive modality in vivo and 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.
Fig.3 a) Chemical reaction of MAL components. b) Theoretical illustration of the cellular distribution of MAL reagents in different cellular compartments
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- Jun Li.; et al, Aggregation-Induced Fluorescence Probe for Monitoring Membrane Potential Changes in Mitochondria. ACS applied materials & interfaces, 2017, 10(15): 12150-12154.
- Arkadiy A.; et al, A bioluminescent probe for longitudinal monitoring of mitochondrial membrane potential. Nature Chemical Biology, 2020, 16(12): 1385-1393.