An efficient PeT based fluorescent probe for mapping mitochondrial oxidative stress produced <i>via</i> the Nox2 pathway

Baruah, Mousumi; Jana, Anal; Ali, Khadem; Mapa, Koyeli; Samanta, Animesh

doi:10.1039/d2tb00356b

Cited by 14 publications

(14 citation statements)

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“…To monitor microenvironments, especially, pH and ΔpH change during mitochondrial damage and fusion with lysosomes (mitolysosomes), small molecular fluorescent probes are indispensable molecular tools . Small molecular probes can offer direct and dynamic visualization and quantitative information of the cellular microenvironment due to their technical simplicity, high sensitivity, and specificity. − Organelle-specific fluorescent probes have been facilitated for monitoring dynamic interactions among organelles with the help of confocal microscopy, which is now at the forefront in high-resolution optical imaging. − Thus, organelle-targetable fluorescent probes that can monitor changes in biomolecular concentration currently are in high demand. A simple design strategy is to attach organelle-targeting moieties with fluorophores.…”

Section: Introductionmentioning

confidence: 99%

PET- and ICT-Based Ratiometric Probe: An Unusual Phenomenon of Morpholine-Conjugated Fluorophore for Mitochondrial pH Mapping during Mitophagy

et al. 2022

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Mitochondrial functions are heavily influenced by acid–base homeostasis. Hence, elucidation of the mitochondrial pH is essential in living cells, and its alterations during pathologies is an interesting question to be addressed. Small molecular fluorescent probes are progressively applied to quantify the mitochondrial pH by fluorescence imaging. Herein, we designed a unique small molecular fluorescent probe, PM-Mor-OH, based on the lipophilic morpholine ligand-conjugated pyridinium derivative of “IndiFluors”. The morpholine-conjugated fluorescent probe usually localized the lysosome. However, herein, we observed unusual phenomena of morpholine-tagged PM-Mor-OH that localized mitochondria explicitly. The morpholine ligand also plays a pivotal role in tuning optical properties via photoinduced electron transfer (PET) during internal pH alteration (ΔpHi). In the mitophagy process, lysosomes engulf damaged mitochondria, leading to ΔpHi, which can be monitored using our probe. It exhibited “ratiometric” emission at single wavelength excitation (ex. 488) and is suitable for monitoring and quantifying the ΔpHi using confocal microscope high-resolution image analysis during mitophagy. The bathochromic emission shifts due to intramolecular charge transfer (ICT) in basic pH were well explained by the time-dependent density functional theory (TD-DFT/PCM). Similarly, the change in the emission ratio (green/red) with pH variations was also validated by the PET process. In addition, PM-Mor-OH can quantify the pH change during oxidative stress induced by rapamycin, mutant A53T α-synuclein-mediated protein misfolding stress in mitochondria, and during starvation. Rapamycin-induced mitophagy was further elucidated by the translocation of mCherry Parkin to damaged mitochondria, which well correlates with our probe. Thus, PM-Mito-OH is a valuable probe for visualizing mitophagy and can act as a suitable tool for the diagnosis of mitochondrial diseases.

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Section: Introductionmentioning

confidence: 99%

PET- and ICT-Based Ratiometric Probe: An Unusual Phenomenon of Morpholine-Conjugated Fluorophore for Mitochondrial pH Mapping during Mitophagy

et al. 2022

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“…First, we checked the effects of ligands on biocompatibility compared to the previously reported PM-S probe . It should be noted that PMS-T was found to be highly biocompatible up to 10 μM for 24 h of incubation (Figure S7).…”

Section: Resultsmentioning

confidence: 99%

“…Recently, our group reported a photoinduced electron transfer (PET)-based, new pentacyclic pyridinium probe, PM-S, 45 which enabled mapping oxidative stress in mitochondria. However, the toxicity at higher concentrations (>10 μM) (Figure S1) limits proceeding further to either in vivo or ex vivo imaging.…”

Section: ■ Introductionmentioning

confidence: 99%

A Photoinduced Electron Transfer-Based Hypochlorite-Specific Fluorescent Probe for Selective Imaging of Proinflammatory M1 in a Rheumatoid Arthritis Model

et al. 2023

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The differentiation of the distinct phenotypes of macrophages is essential for monitoring the stage of inflammatory diseases for accurate diagnosis and treatment. Recent studies revealed that the level of hypochlorite (OCl–) varies from activated M1 macrophages (killing pathogens) to M2 (resolution of inflammation) during inflammation. Thus, we developed a simple and efficient fluorescent probe for discriminating M1 from M0 and M2. Herein, fluorescent-based imaging is applied as an alternative to immunohistochemistry, which is challenging due to the tedious process and high cost. We developed a hypochlorite-specific probe PMS-T to differentiate M1 and M2, employing a metabolism-oriented live-cell distinction. This probe enables the detection of inflammatory rheumatoid arthritis in an ex vivo mouse model. Thus, it can be a potential chemical tool for monitoring inflammatory diseases, including rheumatoid arthritis, that may overcome the existing barriers of immunohistochemistry.

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“…[36][37][38][39][40][41][42] So far, many fluorescent probes have been reported for the detection of viscosity or hypochlorous acid, respectively. [43][44][45][46][47][48][49][50] Although some fluorescent probes have been reported for the detection of viscosity and HOCl (Table S2 †), few fluorescent probes have been reported for the detection of mitochondrial viscosity and HOCl. 34,[51][52][53][54] In addition, near-infrared fluorescent probes are more suitable for biological imaging due to their advantages such as strong tissue penetration, less interference from biological autofluorescence, and less damage to biological samples.…”

Section: Introductionmentioning

confidence: 99%

A dual-response mitochondria-targeted NIR fluorescent probe with large Stokes shift for monitoring viscosity and HOCl in living cells and zebrafish

Yang

Guo

et al. 2023

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An efficient PeT based fluorescent probe for mapping mitochondrial oxidative stress produced via the Nox2 pathway

Abstract: The human innate immune system eliminates the invading pathogens through phagocytosis. The first step of this process is activating the nicotinamide adenine dinucleotide phosphate oxidase (Nox2) that utilizes NADPH to...

Cited by 14 publications

References 49 publications

PET- and ICT-Based Ratiometric Probe: An Unusual Phenomenon of Morpholine-Conjugated Fluorophore for Mitochondrial pH Mapping during Mitophagy

PET- and ICT-Based Ratiometric Probe: An Unusual Phenomenon of Morpholine-Conjugated Fluorophore for Mitochondrial pH Mapping during Mitophagy

A Photoinduced Electron Transfer-Based Hypochlorite-Specific Fluorescent Probe for Selective Imaging of Proinflammatory M1 in a Rheumatoid Arthritis Model

A dual-response mitochondria-targeted NIR fluorescent probe with large Stokes shift for monitoring viscosity and HOCl in living cells and zebrafish

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