A matrix targeted fluorescent probe to monitor mitochondrial dynamics

Ramesh, Madhu; Rajasekhar, Kolla; Gupta, Kavya; Babagond, Vardhaman; Saini, Deepak Kumar; Govindaraju, T.

doi:10.1039/d0ob02128h

Cited by 12 publications

(11 citation statements)

References 60 publications

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“…Aβ42-associated functional abnormalities induce structural defects in mitochondria. In order to analyze the effect of M3 to prevent structural damage, cells were stained with Mito-TG, a mitochondrial probe . The cells were treated with Aβ42 (20 μM) alone and with M3 for 18 h, followed by Mito-TG staining and fluorescence microscopy imaging to visualize the structural changes.…”

Section: Resultsmentioning

confidence: 99%

Rationally Designed Molecules Synergistically Modulate Multifaceted Aβ Toxicity, Microglial Activation, and Neuroinflammation

Ramesh

Balachandra

Andhare

et al. 2022

ACS Chem. Neurosci.

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Synergistic modulation of multifaceted toxicity is the key to tackle multifactorial Alzheimer’s disease (AD). The etiology of AD includes amyloid β (Aβ) amyloidosis, metal ion dyshomeostasis, reactive oxygen species (ROS), oxidative stress, mitochondrial damage, and neuroinflammation. We rationally designed multifunctional modulators by integrating pharmacophores for metal chelation, antioxidant and anti-inflammatory properties, and modulation of Aβ42 aggregation on the naphthalene monoimide (NMI) scaffold. The in vitro and cellular studies of NMIs revealed that M3 synergistically modulates metal-independent and -dependent amyloid toxicity, scavenges ROS, alleviates oxidative stress, and emulates Nrf2-mediated stress response in neuronal cells. M3 effectively reduced structural and functional damage of mitochondria, reduced Cyt c levels, and rescued cells from apoptosis. The biological atomic force microscopy and Western blot analysis revealed the ability of M3 to suppress microglial activation and neuroinflammation through inhibition of the NF-κβ pathway. The synergistic action of M3 is in agreement with our design strategy to develop a multifunctional therapeutic candidate by integrating multiple pharmacophores with distinct structural and functional elements to ameliorate the multifaceted toxicity of AD.

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Section: Resultsmentioning

confidence: 99%

Rationally Designed Molecules Synergistically Modulate Multifaceted Aβ Toxicity, Microglial Activation, and Neuroinflammation

Ramesh

Balachandra

Andhare

et al. 2022

ACS Chem. Neurosci.

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“…In contrast to previous reports of conjugating these salts to deliver cargoes to mitochondria, herein we explored the inherent ability of flavylium probes for organelle‐specific targeting of mitochondria without requiring a carrier like TPP [27] . The fluorescent mitochondrial probes reported in the literature or commercially available can be divided into two categories based on their chemical structure [28] . First category includes cationic dyes (e. g., Rho123) that selectively accumulate in mitochondria depending on negative MMP [29] .…”

Section: Resultsmentioning

confidence: 99%

Mitochondria‐Specific Recognition of G‐Quadruplexes by a Flavylium‐Based Turn‐On Near‐Infrared Rotor Probe

2021

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The ability of mitochondrial DNA (mtDNA) to form G‐quadruplex (GQ) structures suggest their role in diseases involving mitochondrial dysfunction. Detection and visualization of GQ structures specific to mitochondria using fluorescent probes aid in monitoring mtDNA dynamics and homeostasis. Herein, we report the first study of flavylium‐methine rotor probes (FLV1 and FLV3) for discrimination of GQ and non‐GQ structures through turn‐on near infrared (NIR) fluorescence response. The target‐induced disaggregation (TID) and restricted intramolecular rotation (RIR) of FLV1 in the presence of GQ specific to VEGF oncogene leading to significant fluorescence enhancement and delayed lifetime. The colocalization studies with different organelle trackers confirmed selective localization of FLV1 in mitochondria. Nuclease digestion assays showed mitochondria‐specific accumulation of the probe is independent of membrane potential and selectively bind mtDNA GQ. Our study demonstrates the biocompatible and photostable flavylium‐methine dyes as a new category of probes to selectively label mitochondria and target mtDNA GQ in live and fixed cells.

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“…Zhang et al synthesized a dual-activatable NIR-II molecular probe, PN910, to monitor H 2 O 2 and ONOO − in alkaline tissues [ 49 ]. A new class of far-red fluorescent probes, Mito-TG, increased mitochondrial matrix ROS generation levels in different live cells [ 50 ]. More recently, Peng et al developed a BODIPY-based fluorescence probe, BODIPY-T, for sensing O 2 radical dot-level changes in RAW264.7 cells [ 51 ].…”

Section: Oxidoreductase Probementioning

confidence: 99%

Chemical Probes and Activity-Based Protein Profiling for Cancer Research

Mazid

Park

Cheekatla

et al. 2022

IJMS

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Chemical probes can be used to understand the complex biological nature of diseases. Due to the diversity of cancer types and dynamic regulatory pathways involved in the disease, there is a need to identify signaling pathways and associated proteins or enzymes that are traceable or detectable in tests for cancer diagnosis and treatment. Currently, fluorogenic chemical probes are widely used to detect cancer-associated proteins and their binding partners. These probes are also applicable in photodynamic therapy to determine drug efficacy and monitor regulating factors. In this review, we discuss the synthesis of chemical probes for different cancer types from 2016 to the present time and their application in monitoring the activity of transferases, hydrolases, deacetylases, oxidoreductases, and immune cells. Moreover, we elaborate on their potential roles in photodynamic therapy.

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A matrix targeted fluorescent probe to monitor mitochondrial dynamics

Abstract: A far-red turn-on fluorescent probe (Mito-TG) with excellent biocompatibility, photostability, chemical stability targets mitochondrial matrix. The insensitivity of probe under different pH and ROS enabled tracking of mitophagy and Aβ induced mitochondrial dynamics.

Cited by 12 publications

References 60 publications

Rationally Designed Molecules Synergistically Modulate Multifaceted Aβ Toxicity, Microglial Activation, and Neuroinflammation

Rationally Designed Molecules Synergistically Modulate Multifaceted Aβ Toxicity, Microglial Activation, and Neuroinflammation

Mitochondria‐Specific Recognition of G‐Quadruplexes by a Flavylium‐Based Turn‐On Near‐Infrared Rotor Probe

Chemical Probes and Activity-Based Protein Profiling for Cancer Research

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