Journal Article


J H M Prehn
H Düssmann
S Anguissola
C T Hellwig
H J Huber
M Rehm



humans pharmacology metabolism microscopy physiology kinetics flow cytometry mitochondrial membranes tnf related apoptosis inducing ligand hela cells cell membrane structures genetics apoptosis cytochromes c staurosporine drug effects cell membrane permeability enzyme inhibitors models biological

Dynamics of outer mitochondrial membrane permeabilization during apoptosis. (2009)

Abstract Individual cells within a population undergo apoptosis at distinct, apparently random time points. By analyzing cellular mitotic history, we identified that sibling HeLa cell pairs, in contrast to random cell pairs, underwent apoptosis synchronously. This allowed us to use high-speed cellular imaging to investigate mitochondrial outer membrane permeabilization (MOMP), a highly coordinated, rapid process during apoptosis, at a temporal resolution approximately 100 times higher than possible previously. We obtained new functional and mechanistic insight into the process of MOMP: We were able to determine the kinetics of pore formation in the outer mitochondrial membrane from the initiation phase of cytochrome-c-GFP redistribution, and showed differential pore formation kinetics in response to intrinsic or extrinsic apoptotic stimuli (staurosporine, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)). We also detected that the onset of mitochondrial permeabilization frequently proceeded as a wave through the cytosol, and that the frequency of wave occurrence in response to TRAIL was reduced by inhibition of protein kinase CK2. Computational analysis by a partial differential equation model suggested that the spread of permeabilization signals could sufficiently be explained by diffusion-adsorption velocities of locally generated permeabilization inducers. Taken together, our study yielded the first comprehensive analysis of clonal cell-to-cell variability in apoptosis execution and allowed to visualize and explain the dynamics of MOMP in cells undergoing apoptosis.
Collections Ireland -> Royal College of Surgeons in Ireland -> PubMed

Full list of authors on original publication

J H M Prehn, H Düssmann, S Anguissola, C T Hellwig, H J Huber, M Rehm

Experts in our system

Jochen H M Prehn
Royal College of Surgeons in Ireland
Total Publications: 206
Heiko Düssmann
Royal College of Surgeons in Ireland
Total Publications: 45
Christian T Hellwig
Royal College of Surgeons in Ireland
Total Publications: 11
Heinrich J Huber
Royal College of Surgeons in Ireland
Total Publications: 39
Markus Rehm
Royal College of Surgeons in Ireland
Total Publications: 55