A bioluminescent probe for longitudinal monitoring of mitochondrial membrane potential

Bazhin, Arkadiy A.; Sinisi, Riccardo; Marchi, Umberto De; Hermant, Aurélie; Sambiagio, Nicolas; Maric, Tamara; Budin, Ghyslain; Goun, Elena A.

doi:10.1038/s41589-020-0602-1

Cited by 43 publications

(32 citation statements)

References 53 publications

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“…We then investigated the mitochondrial membrane potential after CDN treatment in vivo using mitochondria-activatable luciferin 3 (MAL3) 22 probe ( Supplementary Figure 17 ). The mitochondrial membrane potential significantly decreased at 2 days after CDN treatment (P=0.0176, n=5), then restored to pre-treatment level when imaged at day 8 after treatment ( Fig.…”

Section: Resultsmentioning

confidence: 99%

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Mitochondrial copper depletion suppresses triple-negative breast cancer in mice

et al. 2020

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Depletion of mitochondrial copper, which shifts metabolism from respiration to glycolysis and reduces energy production, is known to be effective against cancer types that depend on oxidative phosphorylation. However, existing copper chelators are too toxic or ineffective for clinical application. Here we develop a safe, mitochondria-targeted, copper-depleting nanoparticle (CDN) and test it against triple-negative breast cancer (TNBC). We show that CDNs decrease oxygen consumption and oxidative phosphorylation, cause a metabolic switch to glycolysis, and reduce ATP production in TNBC cells. This energy deficiency, together with compromised mitochondrial membrane potential and elevated oxidative stress, results in apoptosis. CDNs should be less toxic than existing copper chelators because they favourably deprive copper in the mitochondria in cancer cells instead of systemic depletion. Indeed, we demonstrate low toxicity of CDNs in healthy mice. In three mouse models of TNBC, CDN administration inhibits tumor growth and substantially improves survival. The efficacy and safety of CDNs suggest the potential clinical relevance of this approach.

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Section: Resultsmentioning

confidence: 99%

“…MAL3 probe consists of 2 reagents that result in light production proportional to the level of ΔΨm (TPP-CL2 and azido-TPP1). 22 In a typical ΔΨm imaging experiment, mice received i.v. injection of 100 µl of 700 µM TPP-CL2 solution in the vehicle comprising 0.1% fatty acid-free BSA in PBS.…”

Section: Methodsmentioning

confidence: 99%

Mitochondrial copper depletion suppresses triple-negative breast cancer in mice

et al. 2020

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“…The rate of uncaging and hence rate of formation of active luciferin is proportional to the combined changes in mitochondrial membrane potential and plasma membrane potential. 281 The other type of luciferin probes that have been reported are designed to use the Bioluminescent Enzyme-Induced Electron Transfer (BioLeT) process to modify the light output generated. Bioluminescent Enzyme-Induced Electron Transfer (BioLeT) is analogous to photoinduced electron transfer (PeT) which has often been incorporated in the design of fluorescent probes.…”

Section: Sensing Of Ph Metal Ions Reactive Oxygen Species (Ros) Enmentioning

confidence: 99%

Applications of bioluminescence in biotechnology and beyond

2021

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“…The stability of MMP is conducive to maintaining the normal physiological functions of cells. Apoptosis and oxidative stress are closely related to the stability of MMP [51]. Therefore, we also investigated the effect of PCu on the membrane stability of mitochondria by JC-1 fluorescent staining.…”

Section: Pcu Inhibited Cu 2+ -Mediated Aβ Deposition In Vitromentioning

confidence: 99%

A Novel Cu(II)-Binding Peptide Identified by Phage Display Inhibits Cu2+-Mediated Aβ Aggregation

Zhang

Zhong

et al. 2021

IJMS

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Copper (Cu) has been implicated in the progression of Alzheimer’s disease (AD), and aggregation of Cu and amyloid β peptide (Aβ) are considered key pathological features of AD. Metal chelators are considered to be potential therapeutic agents for AD because of their capacity to reduce metal ion-induced Aβ aggregation through the regulation of metal ion distribution. Here, we used phage display technology to screen, synthesize, and evaluate a novel Cu(II)-binding peptide that specifically blocked Cu-triggered Aβ aggregation. The Cu(II)-binding peptide (S-A-Q-I-A-P-H, PCu) identified from the phage display heptapeptide library was used to explore the mechanism of PCu inhibition of Cu2+-mediated Aβ aggregation and Aβ production. In vitro experiments revealed that PCu directly inhibited Cu2+-mediated Aβ aggregation and regulated copper levels to reduce biological toxicity. Furthermore, PCu reduced the production of Aβ by inhibiting Cu2+-induced BACE1 expression and improving Cu(II)-mediated cell oxidative damage. Cell culture experiments further demonstrated that PCu had relatively low toxicity. This Cu(II)-binding peptide that we have identified using phage display technology provides a potential therapeutic approach to prevent or treat AD.

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A bioluminescent probe for longitudinal monitoring of mitochondrial membrane potential

Cited by 43 publications

References 53 publications

Mitochondrial copper depletion suppresses triple-negative breast cancer in mice

Mitochondrial copper depletion suppresses triple-negative breast cancer in mice

Applications of bioluminescence in biotechnology and beyond

A Novel Cu(II)-Binding Peptide Identified by Phage Display Inhibits Cu2+-Mediated Aβ Aggregation

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