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Optogenetic Apoptosis: Light‐Triggered Cell Death
Author(s) -
Hughes Robert M.,
Freeman David J.,
Lamb Kelsey N.,
Pollet Rebecca M.,
Smith Weston J.,
Lawrence David S.
Publication year - 2015
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201506346
Subject(s) - optogenetics , apoptosis , microbiology and biotechnology , programmed cell death , caspase , mitochondrion , chemistry , cleavage (geology) , bcl 2 associated x protein , biology , biophysics , caspase 3 , biochemistry , neuroscience , paleontology , fracture (geology)
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.