A Small Molecule that Induces Intrinsic Pathway Apoptosis with Unparalleled Speed

Rahul Palchaudhuri, Michael J. Lambrecht, Rachel C. Botham, Kathryn C. Partlow, Tjakko J. van Ham, Karson S. Putt, Laurie T. Nguyen, Seok Ho Kim, Randall T. Peterson, Timothy M. Fan, Paul J. Hergenrother

Research output: Contribution to journalArticlepeer-review

Abstract

Apoptosis is generally believed to be a process that requires 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 critical roles 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 in vivo 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.

Original languageEnglish (US)
Pages (from-to)2027-2036
Number of pages10
JournalCell Reports
Volume13
Issue number9
DOIs
StatePublished - Dec 1 2015

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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