title: 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.
authors.affiliation: Department of Chemistry, Division of Chemical Biology and Medicinal Chemistry, Department of Pharmacology, University of North Carolina, Chapel Hill, NC 27599 (USA). rhughes@email.unc.edu.
authors.forename: Robert M
authors.initials: RM
authors.lastname: Hughes
authors.affiliation: Department of Chemistry, Division of Chemical Biology and Medicinal Chemistry, Department of Pharmacology, University of North Carolina, Chapel Hill, NC 27599 (USA).
authors.forename: David J
authors.initials: DJ
authors.lastname: Freeman
authors.affiliation: Department of Chemistry, Division of Chemical Biology and Medicinal Chemistry, Department of Pharmacology, University of North Carolina, Chapel Hill, NC 27599 (USA).
authors.forename: Kelsey N
authors.initials: KN
authors.lastname: Lamb
authors.affiliation: Department of Chemistry, Division of Chemical Biology and Medicinal Chemistry, Department of Pharmacology, University of North Carolina, Chapel Hill, NC 27599 (USA).
authors.forename: Rebecca M
authors.initials: RM
authors.lastname: Pollet
authors.affiliation: Department of Chemistry, Division of Chemical Biology and Medicinal Chemistry, Department of Pharmacology, University of North Carolina, Chapel Hill, NC 27599 (USA).
authors.forename: Weston J
authors.initials: WJ
authors.lastname: Smith
authors.affiliation: Department of Chemistry, Division of Chemical Biology and Medicinal Chemistry, Department of Pharmacology, University of North Carolina, Chapel Hill, NC 27599 (USA). lawrencd@email.unc.edu.
authors.forename: David S
authors.initials: DS
authors.lastname: Lawrence
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000528:radiation effects*; D053148:Caspase 3 / Q000378:metabolism; D020169:Caspases / Q000378:metabolism; D002460:Cell Line; D006801:Humans; D008027:Light; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism / Q000528:radiation effects*; D062308:Optogenetics; D015202:Protein Engineering; D051028:bcl-2-Associated X Protein / Q000235:genetics* / Q000378:metabolism
chemical_list: D051028:bcl-2-Associated X Protein; D053148:Caspase 3; D020169:Caspases
keywords: apoptosis; optogenetics; photochemistry; protein engineering; synthetic biology