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Selective uncoupling of individual mitochondria within a cell using a mitochondria-targeted photoactivated protonophore.

ABSTRACT: Depolarization of an individual mitochondrion or small clusters of mitochondria within cells has been achieved using a photoactivatable probe. The probe is targeted to the matrix of the mitochondrion by an alkyltriphenylphosphonium lipophilic cation and releases the protonophore 2,4-dinitrophenol locally in predetermined regions in response to directed irradiation with UV light via a local photolysis system. This also provides a proof of principle for the general temporally and spatially controlled release of bioactive molecules, pharmacophores, or toxins to mitochondria with tissue, cell, or mitochondrion specificity.

SUBMITTER: Chalmers S

PROVIDER: S-EPMC3260739 | biostudies-literature | 2012 Jan

REPOSITORIES: biostudies-literature

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Selective uncoupling of individual mitochondria within a cell using a mitochondria-targeted photoactivated protonophore.

Chalmers Susan S Caldwell Stuart T ST Quin Caroline C Prime Tracy A TA James Andrew M AM Cairns Andrew G AG Murphy Michael P MP McCarron John G JG Hartley Richard C RC

Journal of the American Chemical Society 20111230 2

Depolarization of an individual mitochondrion or small clusters of mitochondria within cells has been achieved using a photoactivatable probe. The probe is targeted to the matrix of the mitochondrion by an alkyltriphenylphosphonium lipophilic cation and releases the protonophore 2,4-dinitrophenol locally in predetermined regions in response to directed irradiation with UV light via a local photolysis system. This also provides a proof of principle for the general temporally and spatially control ...[more]

PMID: 22239373

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Penetrating cation/fatty acid anion pair as a mitochondria-targeted protonophore.

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Selective Functions of Individual Zinc Fingers Within the DNA-Binding Domain of Ikaros

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2013-09-08 | E-GEOD-33693 | biostudies-arrayexpress

Selective Functions of Individual Zinc Fingers Within the DNA-Binding Domain of Ikaros

Project description:This SuperSeries is composed of the SubSeries listed below.

2013-09-08 | GSE33693 | GEO

Mitochondria selective S-nitrosation by mitochondria-targeted S-nitrosothiol protects against post-infarct heart failure in mouse hearts.

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Uncoupling of PARP1 Trapping and Inhibition Using Selective PARP1 Degradation

Project description:PARP1 inhibitors (PARPi) are known to kill tumor cells via two mechanisms (i.e., PARP1 catalytic inhibition vs. PARP1 trapping). The relative contribution of these two pathways in mediating the cytotoxicity of PARPi, however, is incompletely understood. Here we designed a series of small molecule PARP degraders. Treatment with one such compound iRucaparib (1) results in highly efficient and specific PARP1 degradation. iRucaparib blocks the enzymatic activity of PARP1 in vitro, and PARP1-mediated PARylation signaling in intact cells. This strategy mimics PARP1 genetic depletion, which enables the pharmacological decoupling of PARP1 inhibition from PARP1 trapping. Finally, by depleting PARP1, iRucaparib protects muscle cells and primary cardiomyocytes from DNA damage-induced energy crisis and cell death. In summary, these compounds represent “non-trapping” PARP1 degraders that block both the catalytic activity and scaffolding effects of PARP1, providing an ideal approach for the amelioration of the various pathological conditions caused by PARP1 hyperactivation.

2019-08-01 | PXD014837 | Pride

Uncoupling of PARP1 Trapping and Inhibition Using Selective PARP1 Degradation

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