Optogenetic Apoptosis: Light-Triggered Cell Death
Corresponding Author
Prof. Robert M. Hughes
Department of Chemistry, Division of Chemical Biology and Medicinal Chemistry, Department of Pharmacology, University of North Carolina, Chapel Hill, NC 27599 (USA)
Department of Chemistry, Division of Chemical Biology and Medicinal Chemistry, Department of Pharmacology, University of North Carolina, Chapel Hill, NC 27599 (USA)Search for more papers by this authorDavid J. Freeman
Department of Chemistry, Division of Chemical Biology and Medicinal Chemistry, Department of Pharmacology, University of North Carolina, Chapel Hill, NC 27599 (USA)
Search for more papers by this authorKelsey N. Lamb
Department of Chemistry, Division of Chemical Biology and Medicinal Chemistry, Department of Pharmacology, University of North Carolina, Chapel Hill, NC 27599 (USA)
Search for more papers by this authorRebecca M. Pollet
Department of Chemistry, Division of Chemical Biology and Medicinal Chemistry, Department of Pharmacology, University of North Carolina, Chapel Hill, NC 27599 (USA)
Search for more papers by this authorWeston J. Smith
Department of Chemistry, Division of Chemical Biology and Medicinal Chemistry, Department of Pharmacology, University of North Carolina, Chapel Hill, NC 27599 (USA)
Search for more papers by this authorCorresponding Author
Prof. David S. Lawrence
Department of Chemistry, Division of Chemical Biology and Medicinal Chemistry, Department of Pharmacology, University of North Carolina, Chapel Hill, NC 27599 (USA)
Department of Chemistry, Division of Chemical Biology and Medicinal Chemistry, Department of Pharmacology, University of North Carolina, Chapel Hill, NC 27599 (USA)Search for more papers by this authorCorresponding Author
Prof. Robert M. Hughes
Department of Chemistry, Division of Chemical Biology and Medicinal Chemistry, Department of Pharmacology, University of North Carolina, Chapel Hill, NC 27599 (USA)
Department of Chemistry, Division of Chemical Biology and Medicinal Chemistry, Department of Pharmacology, University of North Carolina, Chapel Hill, NC 27599 (USA)Search for more papers by this authorDavid J. Freeman
Department of Chemistry, Division of Chemical Biology and Medicinal Chemistry, Department of Pharmacology, University of North Carolina, Chapel Hill, NC 27599 (USA)
Search for more papers by this authorKelsey N. Lamb
Department of Chemistry, Division of Chemical Biology and Medicinal Chemistry, Department of Pharmacology, University of North Carolina, Chapel Hill, NC 27599 (USA)
Search for more papers by this authorRebecca M. Pollet
Department of Chemistry, Division of Chemical Biology and Medicinal Chemistry, Department of Pharmacology, University of North Carolina, Chapel Hill, NC 27599 (USA)
Search for more papers by this authorWeston J. Smith
Department of Chemistry, Division of Chemical Biology and Medicinal Chemistry, Department of Pharmacology, University of North Carolina, Chapel Hill, NC 27599 (USA)
Search for more papers by this authorCorresponding Author
Prof. David S. Lawrence
Department of Chemistry, Division of Chemical Biology and Medicinal Chemistry, Department of Pharmacology, University of North Carolina, Chapel Hill, NC 27599 (USA)
Department of Chemistry, Division of Chemical Biology and Medicinal Chemistry, Department of Pharmacology, University of North Carolina, Chapel Hill, NC 27599 (USA)Search for more papers by this authorAbstract
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.
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