FRET-based ratiometric fluorescent probes for selective Fe3+ sensing and their applications in mitochondria

Chen, Wendan; Gong, Weitao; Ye, Zhiqiang; Yuan, Lin; Ning, Guiling

doi:10.1039/c3dt50832c

Cited by 62 publications

(38 citation statements)

References 39 publications

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“…[64] Photophysical examinations demonstrated as elective turn-on (10-fold) response,w hile co-staining showed that Mito-CS1 localized in mitochondria in HEK 293T cells ( Figure 4). [66] Upon addition of Fe 3+ ,t he hydrazine interacted with the metal species,t hus opening the ring and restoring the conjugate structure of the rhodamine scaffold. [64] In another case,adeprotection strategy utilizing spirocyclic rhodamine was also applied to develop am itochondriatargeting Cu + probe (14 b,Scheme 3).…”

Section: Mitafps For Metal Ions and The Ph Valuementioning

confidence: 99%

“…Further molecular imaging studies indicated that Mito-CS1 was able to detect changes in the concentration of labile mitochondrial Cu + in both HEK 293T cells and human fibroblasts.I na ddition, Mito-CS1 showed real applications by imaging cytochrome c oxidase 1a nd 2( SCO1 and SCO2) mutations in human fibroblasts,both of which cause variations in the Cu + level. [66] [65] Very recently,C hen et al designed the ratiometric probe RNP1 (15,S cheme 3) for mitochondrial Fe 3+ based on aF RET mechanism.…”

Section: Mitafps For Metal Ions and The Ph Valuementioning

confidence: 99%

“…As as traightforward strategy,aTPPconjugated naphthalene chromophore was integrated into ar hodamine platform with as pirolactam ring through ah ydrazine linker. [66] Upon addition of Fe 3+ ,t he hydrazine interacted with the metal species,t hus opening the ring and restoring the conjugate structure of the rhodamine scaffold. Accordingly,F RET occurred from the naphthalene to the rhodamine,thereby leading to ared-shift of the emission.…”

Section: Mitafps For Metal Ions and The Ph Valuementioning

confidence: 99%

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Discerning the Chemistry in Individual Organelles with Small‐Molecule Fluorescent Probes

et al. 2016

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Principle has it that even the most advanced super-resolution microscope would be futile in providing biological insight into subcellular matrices without well-designed fluorescent tags/probes. Developments in biology have increasingly been boosted by advances of chemistry, with one prominent example being small-molecule fluorescent probes that not only allow cellular-level imaging, but also subcellular imaging. A majority, if not all, of the chemical/biological events take place inside cellular organelles, and researchers have been shifting their attention towards these substructures with the help of fluorescence techniques. This Review summarizes the existing fluorescent probes that target chemical/biological events within a single organelle. More importantly, organelle-anchoring strategies are described and emphasized to inspire the design of new generations of fluorescent probes, before concluding with future prospects on the possible further development of chemical biology.

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Section: Mitafps For Metal Ions and The Ph Valuementioning

confidence: 99%

Section: Mitafps For Metal Ions and The Ph Valuementioning

confidence: 99%

Section: Mitafps For Metal Ions and The Ph Valuementioning

confidence: 99%

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Discerning the Chemistry in Individual Organelles with Small‐Molecule Fluorescent Probes

et al. 2016

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“…To further justify these findings, we developed a novel fluorescence iron sensor which measures mitochondrial iron (9). An enhanced far red fluorescence was observed using our RNP1 dye on the basis of FRET mechanism in H9C2 cells treated with DOX (10 M) for 24 h. However, the same dose and duration of the treatment with DOX did not produce a fluorescent signal in our FXN-OE cells in the presence of RNP1 (Fig.…”

Section: Dox-mediated Reduction In Fxn Alters Mitochondrial Iron Homementioning

confidence: 99%

“…In the presence of iron, a deep red fluorescence was obtained. The dye exhibits pseudo-large stokes shift based on a fluorescence resonance energy transfer (FRET) mechanism and the naphthalene chromophore (9). Cultured H9C2 and FXN-OE cardiomyoblasts were treated with or without DOX (10 M) for 24 h and incubated with RNP1 and colocalized with MitoTracker Green FM (1 M) for 30 min.…”

Section: Mitochondrial Iron Detection: Fluorescence Resonance Energy mentioning

confidence: 99%

The role of frataxin in doxorubicin-mediated cardiac hypertrophy

Mouli

Nanayakkara

AlAlasmari

et al. 2015

American Journal of Physiology-Heart and Circulatory Physiology

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(DOX) is a highly effective anti-neoplastic agent; however, its cumulative dosing schedules are clinically limited by the development of cardiotoxicity. Previous studies have attributed the cause of DOXmediated cardiotoxicity to mitochondrial iron accumulation and the ensuing reactive oxygen species (ROS) formation. The present study investigates the role of frataxin (FXN), a mitochondrial iron-sulfur biogenesis protein, and its role in development of DOX-mediated mitochondrial dysfunction. Athymic mice treated with DOX (5 mg/ kg, 1 dose/wk with treatments, followed by 2-wk recovery) displayed left ventricular hypertrophy, as observed by impaired cardiac hemodynamic performance parameters. Furthermore, we also observed significant reduction in FXN expression in DOX-treated animals and H9C2 cardiomyoblast cell lines, resulting in increased mitochondrial iron accumulation and the ensuing ROS formation. This observation was paralleled in DOX-treated H9C2 cells by a significant reduction in the mitochondrial bioenergetics, as observed by the reduction of myocardial energy regulation. Surprisingly, similar results were observed in our FXN knockdown stable cell lines constructed by lentiviral technology using short hairpin RNA. To better understand the cardioprotective role of FXN against DOX, we constructed FXN overexpressing cardiomyoblasts, which displayed cardioprotection against mitochondrial iron accumulation, ROS formation, and reduction of mitochondrial bioenergetics. Lastly, our FXN overexpressing cardiomyoblasts were protected from DOX-mediated cardiac hypertrophy. Together, our findings reveal novel insights into the development of DOX-mediated cardiomyopathy.anthracyclines; frataxin; cardiomyopathy; iron overload; mitochondrial damage; oxidative stress DOXORUBICIN (DOX) IS ONE OF the most widely used anti-neoplastic agents used for the treatment of a wide range of solid tumors and leukemia in children and adults (10,36,40). Despite its therapeutic usage, the clinical use of DOX is severely limited due to its cumulative dose-dependent cardiotoxicity, which develops over time into congestive heart failure (30). During this process, mitochondrial dysfunction has been observed to be fundamentally involved in the development of heart failure due to the dysregulation of mitochondrial bioenergetics and the generation of intracellular reactive oxygen species (ROS). The mechanism of DOX-induced cardiotoxicity at the cellular and subcellular levels is highly debatable. However, much attention has been attributed to the DOX-mediated formation of mitochondrial ROS. Although the role of iron has not been emphasized in the failing myocardial model, the role of iron in the formation of ROS has gained significance at the clinical setting with the usage of dexrazoxane (DXZ). DXZ, an iron chelator, is known to induce degradation of topo2␤ and prevent the DOX-mediated initiation of the DNA damage signal, H2AX-␥, in H9C2 cardiomyoblasts (28). However, the use of DXZ has been limited due to its interference with antitumor acti...

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Wahrnehmung der chemischen Prozesse in einzelnen Organellen mit niedermolekularen Fluoreszenzsonden

et al. 2016

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Ohne genau durchdachte Fluoreszenzmarker/‐sonden kann auch das fortschrittlichste hochauflösende Mikroskopieverfahren keinen Einblick in subzelluläre Matrizes geben. Die Entwicklung der Biologie wurde in zunehmendem Maße durch Fortschritte im Bereich der Chemie vorangetrieben. Ein prominentes Beispiel hierfür sind niedermolekulare Fluoreszenzsonden, die nicht nur die Bildgebung auf zellulärer Ebene ermöglichen, sondern auch subzelluläre Abbildungen. Die meisten chemischen/biologischen Ereignisse finden innerhalb von Zellorganellen statt, sodass diese Substrukturen zunehmend mithilfe von Fluoreszenzverfahren untersucht wurden. Dieser Aufsatz fasst die vorhandenen Fluoreszenzsonden zusammen, die auf chemische/biologische Geschehnisse innerhalb einzelner Organellen zielen. Darüber hinaus werden Strategien zur Verankerung an den Organellen vorgestellt, um das Design neuer Fluoreszenzsonden anzuregen. Abschließend werden die Zukunftsaussichten für weitere Entwicklungen in der chemischen Biologie diskutiert.

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FRET-based ratiometric fluorescent probes for selective Fe3+ sensing and their applications in mitochondria

Cited by 62 publications

References 39 publications

Discerning the Chemistry in Individual Organelles with Small‐Molecule Fluorescent Probes

Discerning the Chemistry in Individual Organelles with Small‐Molecule Fluorescent Probes

The role of frataxin in doxorubicin-mediated cardiac hypertrophy

Wahrnehmung der chemischen Prozesse in einzelnen Organellen mit niedermolekularen Fluoreszenzsonden

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