BH3 profiling--measuring integrated function of the mitochondrial apoptotic pathway to predict cell fate decisions.

Apoptosis is a form of programmed cell death that is controlled at the mitochondrion by the BCL-2 family of proteins. While much has been learned about the structure and function of these proteins over the past two decades, the important goal of predicting cell fate decisions in response to toxic stimuli is largely unrealized. BH3 profiling is a functional approach that can be used to predict cellular responses to stimuli based on measuring the response of mitochondria to perturbation by a panel of BH3 domain peptides. BH3 profiling has proven useful in identifying and understanding cellular dependence on individual anti-apoptotic proteins like BCL-2 or MCL-1. Consequently, it can also be used to predict cellular response to chemotherapy agents such as ABT-737 that target these individual proteins.