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Cell Rep. 2015 Dec 1;13(9):2027-36. doi: 10.1016/j.celrep.2015.10.042. Epub 2015 Nov 19.

A Small Molecule that Induces Intrinsic Pathway Apoptosis with Unparalleled Speed.

Author information

1
Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
2
Cardiovascular Research Center and Division of Cardiology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA; Broad Institute, Cambridge, MA 02142, USA.
3
Department of Biochemistry, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
4
Department of Veterinary Clinical Medicine, University of Illinois at Urbana-Champaign, Urbana, IL 61802, USA.
5
Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA. Electronic address: hergenro@illinois.edu.

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.

PMID:
26655912
PMCID:
PMC4683402
DOI:
10.1016/j.celrep.2015.10.042
[Indexed for MEDLINE]
Free PMC Article

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