Point of No Return—What Is the Threshold of Mitochondria With Permeability Transition in Cells to Trigger Cell Death
2025

Threshold of Mitochondria With Permeability Transition in Cells to Trigger Cell Death

publication Evidence: high

Author Information

Author(s): Kritskaya Kristina A., Stelmashchuk Olga A., Abramov Andrey Y.

Hypothesis

Is there a threshold in the number of mitochondria with mPTP that induces cell death and how is this mechanism regulated in different tissues?

Conclusion

Different tissues require specific numbers of mitochondria with PTP opening to induce apoptosis, correlating with the proapoptotic/antiapoptotic protein expression ratio.

Supporting Evidence

  • Apoptosis was correlated with 80%-90% mitochondrial signal loss in neural cells but only 35% in fibroblasts.
  • In BT-474 cancer cells, over 90% of mitochondria must open mPTP before apoptosis becomes obvious.
  • The number of mitochondria with mPTP that induce cell death did not correlate with total expression levels of proapoptotic proteins.

Takeaway

This study found that different types of cells need different amounts of damaged mitochondria to start dying, which is important for understanding how cells live and die.

Methodology

Simultaneous measurements of mitochondrial membrane potential and caspase-3 activation were used to study the number of mitochondria with calcium-induced mPTP opening necessary for apoptosis in various cell types.

Limitations

The study utilized cells from different species, which may introduce variability in calcium handling and mitochondrial function.

Participant Demographics

The study involved rat primary cortical neurons, astrocytes, human skin fibroblasts, and BT-474 cancer cells.

Statistical Information

Statistical Significance

p<0.05

Digital Object Identifier (DOI)

10.1002/jcp.31521

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