Type

Other / n/a

Authors

Jochen HM Prehn
Heiko Düssmann
Sergio Anguissola
Christian T Hellwig
Heinrich J Huber
Markus Rehm

Subjects

Biochemistry

Topics
microscopy physiology humans tnf related apoptosis inducing ligand kinetics flow cytometry staurosporine cell membrane structures cell membrane permeability cytochromes c apoptosis models biological physics mitochondrial membranes hela cells enzyme inhibitors 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 -> Physiology and Medical Physics Articles
Ireland -> Royal College of Surgeons in Ireland -> Department of Physiology and Medical Physics

Full list of authors on original publication

Jochen HM Prehn, Heiko Düssmann, Sergio Anguissola, Christian T Hellwig, Heinrich J Huber, Markus Rehm

Experts in our system

1
Jochen H M Prehn
Royal College of Surgeons in Ireland
Total Publications: 206
 
2
Heiko Düssmann
Royal College of Surgeons in Ireland
Total Publications: 45
 
3
Christian T Hellwig
Royal College of Surgeons in Ireland
Total Publications: 11
 
4
Heinrich J Huber
Royal College of Surgeons in Ireland
Total Publications: 39
 
5
Markus Rehm
Royal College of Surgeons in Ireland
Total Publications: 55