Super-Resolution Monitoring of Mitochondrial Dynamics upon Time-Gated Photo-Triggered Release of Nitric Oxide

Abstract

Nitric oxide (NO) potentially plays a regulatory role in mitochondrial fusion and fission, which are vital to cell survival and implicated in health, disease, and aging. Molecular tools facilitating the study of the relationship between NO and mitochondrial dynamics are in need. We have recently developed a novel NO donor (NOD550). Upon photoactivation, NOD550 decomposes to release two NO molecules and a fluorophore. The NO release could be spatially mapped with subdiffraction resolution and with a temporal resolution of 10 s. Due to the preferential localization of NOD550 at mitochondria, morphology and dynamics of mitochondria could be monitored upon NO release from NOD550.

Fluorescent Nitric Oxide Photodonors Based on BODIPY and Rhodamine Antennae

“…This species is very stable due to the presence of the electron drawing nitro and trifluoromethyl groups, is expected to be basically insensitive to the presence of oxygen and that can evolve to the stable photoproducts 1 a and 2 a via H‐transfer from solvent. This picture is in excellent agreement with the identical photolytic behavior we observed in aerobic and anaerobic conditions and accords well to what already reported the photoproducts formed by other N ‐nitrosamine after loss of NO . Furthermore, our proposal is supported by the considerable changes in free energy for the photoinduced electron transfer processes, Δ G ≅−0.5 eV and −0.3 eV for compound 1 and 2 , estimated by the Rehm‐Weller equation [Equation ]: …”

“…Furthermore, the quantum efficiency, expressed as the product of ϵ max Φ NO , is approximately 2800, a value much more superior to those reported for other organic NOPDs –. In the case of 2 , the value observed for Φ NO is similar to other Rhodamine derivatives that, however, exhibit fluorescence quantum yields more than one order of magnitude lower than compound 2 –…”

“…However, despite some BODIPY‐based NOPDs exhibited good fluorescence emission, the NO photorelease quantum yield ( Φ NO ) was on the order of 10 −3 and the quantum efficiency ( ϵ max Φ NO ) did not exceed 550 –. On the other hand, in the case of Rhodamine‐based NOPDs the typical fluorescence emission of this fluorogenic unit is dramatically quenched before the NO photorelease takes place –…”

A High‐Performing Metal‐Free Photoactivatable Nitric Oxide Donor with a Green Fluorescent Reporter

“…The identical nature of the photoproduct observed under both aerobic and anaerobic conditions, is in good agreement with the formation of the anilinyl radical as logical key intermediate after the loss of NO via homolytic N‐NO cleavage. In fact, this species is expected to be basically insensitive to the presence of oxygen and can evolve to the stable photoproducts NBF via H‐transfer from solvent, in excellent agreement with the mechanism already reported for other N ‐nitrosamine after loss of NO …”

A Photoactivable Formaldehyde Donor with Fluorescence Monitoring Reveals Threshold to Arrest Cell Migration

“…Photoactivatable donors for reactive oxygen, 1,2 nitrogen, [3][4][5][6][7] sulfur, [8][9][10] and carbonyl species, [11][12][13] as well as metal ions 14 have been reported. Recent developments have led to photoactivatable donors equipped with the ability to monitor analyte release through fluorescence 12,13,[15][16][17][18] or photoacoustic 19 readouts. Despite these advances we have recognized that there are two major voids in this area.…”