(1) Functional Genomics Unit, Barts and the London School of Medicine and Dentistry, London, UK;(2) Cancer Research and Cell Biology, Queens University, U Floor, City Hospital, Lisburn Road, Belfast, BT9 7AB, Northern Ireland
Abstract:
Robust quantitative estimation of average whole cell mitochondrial dysfunction is a useful tool for assessing sensitivity to apoptotic stimuli induced either by novel agents, or following manipulation of apoptotic threshold by pharmacological or functional genomics approaches. We have mathematically modelled the kinetics of whole cell mitochondrial membrane potential depolarisation within a population of cells as a Bernouli transition. An exponential distribution enables the median latency preceding mitochondrial membrane potential disispation to be derived. The kinetic model can be fitted to in vitro single cell resolution data derived from kinetic flow cytometric studies by non-linear regression. We propose that kinetic determination of cumulative frequency distibutions provides a useful approach for estimating apoptosis sensitivity across cell populations over short time-frames.