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Optogenetic apoptosis: light-triggered cell death.

ABSTRACT: An optogenetic Bax has been designed that facilitates light-induced apoptosis. We demonstrate that mitochondrial recruitment of a genetically encoded light-responsive Bax results in the release of mitochondrial proteins, downstream caspase-3 cleavage, changes in cellular morphology, and ultimately cell death. Mutagenesis of a key phosphorylatable residue or modification of the C-terminus mitigates background (dark) levels of apoptosis that result from Bax overexpression. The mechanism of optogenetic Bax-mediated apoptosis was explored using a series of small molecules known to interfere with various steps in programmed cell death. Optogenetic Bax appears to form a mitochondrial apoptosis-induced channel analogous to that of endogenous Bax.

SUBMITTER: Hughes RM

PROVIDER: S-EPMC4819321 | biostudies-literature | 2015 Oct

REPOSITORIES: biostudies-literature

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Optogenetic apoptosis: light-triggered cell death.

Hughes Robert M RM Freeman David J DJ Lamb Kelsey N KN Pollet Rebecca M RM Smith Weston J WJ Lawrence David S DS

Angewandte Chemie (International ed. in English) 20150825 41

An optogenetic Bax has been designed that facilitates light-induced apoptosis. We demonstrate that mitochondrial recruitment of a genetically encoded light-responsive Bax results in the release of mitochondrial proteins, downstream caspase-3 cleavage, changes in cellular morphology, and ultimately cell death. Mutagenesis of a key phosphorylatable residue or modification of the C-terminus mitigates background (dark) levels of apoptosis that result from Bax overexpression. The mechanism of optogen ...[more]

PMID: 26418181

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