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Updated: Jun 26, 2026

Assessment of Open Probability of the Mitochondrial Permeability Transition Pore in the Setting of Coenzyme Q Excess
Published on: June 1, 2022
Dynamics of outer mitochondrial membrane permeabilization during apoptosis
M Rehm1, H J Huber, C T Hellwig
1Department of Physiology and Medical Physics, Royal College of Surgeons in Ireland, Dublin 2, Ireland. mrehm@rcsi.ie
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.
Insights
Sibling cells undergo programmed cell death together, revealing new insights into mitochondrial outer membrane permeabilization (MOMP) dynamics during apoptosis. This synchronized cell death allows for high-resolution imaging of MOMP.
Area of Science:
- Cell Biology
- Biophysics
Background:
- Apoptosis, or programmed cell death, is a fundamental biological process.
- Individual cells initiate apoptosis at seemingly random times.
- Mitochondrial outer membrane permeabilization (MOMP) is a critical and rapid event in apoptosis.
Purpose of the Study:
- To investigate the dynamics of MOMP at unprecedented temporal resolution.
- To analyze clonal cell-to-cell variability in apoptosis execution.
- To elucidate the mechanisms underlying MOMP propagation.
Main Methods:
- High-speed cellular imaging of synchronized sibling HeLa cell pairs.
- Analysis of cytochrome-c-GFP redistribution kinetics.
- Computational modeling using partial differential equations.
- Pharmacological inhibition of protein kinase CK2.
Main Results:
- Sibling cells exhibit synchronous apoptosis, enabling high-resolution MOMP studies.
- Determined kinetics of pore formation during MOMP, differentiating responses to intrinsic and extrinsic apoptotic stimuli.
- Observed MOMP spreading as a wave, with reduced frequency upon protein kinase CK2 inhibition.
- Computational models support diffusion-adsorption mechanisms for MOMP signal propagation.
Conclusions:
- Synchronized apoptosis in sibling cells provides a novel system for studying MOMP.
- The study offers detailed mechanistic insights into MOMP dynamics and propagation.
- Identified protein kinase CK2 as a modulator of MOMP wave frequency.
Related Concept Videos
Mitochondrial Membranes
Mitochondrial Membranes
The Intrinsic Apoptotic Pathway
Apoptosis
Cellular Injury V: Apoptosis and Autophagy
The Inner Mitochondrial Membrane

