Apoptosis is generally believed to be a process thatrequires several hours, in contrast to non-programmed forms of cell death that can occur in minutes. Our findings challenge the time-consuming nature of apoptosis as we describe the discovery and characterization of a small molecule, named Raptinal, which initiates intrinsic pathway caspase-dependent apoptosis within minutes in multiple cell lines. Comparison to a mechanistically diverse panel of apoptotic stimuli reveals that Raptinal-induced apoptosis proceeds with unparalleled speed. The rapid phenotype enabled identification of the criticalroles of mitochondrial voltage-dependent anion channel function, mitochondrial membrane potential/coupled respiration, and mitochondrial complex I, III, and IV function for apoptosis induction. Use of Raptinal in whole organisms demonstrates its utility for studying apoptosis invivo for a variety of applications. Overall, rapid inducers of apoptosis are powerful tools that will be used in a variety of settings to generate further insight into the apoptotic machinery. Palchaudhuri etal. describe the discovery of a small molecule called "Raptinal" that induces unusually rapid apoptotic cell death via the intrinsic pathway. Their work describes the utility of Raptinal as a tool for apoptosis induction relative to other available small molecules.

doi.org/10.1016/j.celrep.2015.10.042, hdl.handle.net/1765/86709
Cell Reports
Erasmus MC: University Medical Center Rotterdam

Palchaudhuri, R., Lambrecht, M. J., Botham, R. C., Partlow, K. C., vanHam, T. J., Putt, K. S., … Hergenrother, P. J. (2015). A Small Molecule that Induces Intrinsic Pathway Apoptosis with Unparalleled Speed. Cell Reports, 13(9), 2027–2036. doi:10.1016/j.celrep.2015.10.042