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Distinct alterations in mitochondrial mass and function characterize different models of apoptosis
S Camilleri-Broët1, H Vanderwerff, E Caldwell
1Division of Clinical Research and Molecular Medicine, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA.
Experimental Cell Research
|April 2, 1998
Summary
Mitochondrial changes during apoptosis vary by cell type. Some cells increase mitochondrial mass with decreased membrane potential, while others show reduced potential without proliferation, indicating dysfunctional mitochondria contribute to cell death.
Area of Science:
- Cell Biology
- Biochemistry
- Molecular Biology
Background:
- Apoptosis involves early events like reduced mitochondrial membrane potential (Δψm) and reactive oxygen species generation.
- Mitochondrial dynamics are crucial in regulating cell death pathways.
Purpose of the Study:
- To investigate distinct mitochondrial alterations in two models of apoptosis.
- To correlate mitochondrial mass and membrane potential changes with cell death.
Main Methods:
- Utilized Chinese hamster ovary (CHO) cells and 2B4 T-cell hybridoma cells.
- Induced apoptosis using aphidicolin (CHO) and dexamethasone (2B4 T-cells).
- Assessed mitochondrial mass, number, and membrane potential (Δψm) via flow cytometry and fluorescent microscopy.
Main Results:
- Aphidicolin-treated CHO cells showed increased mitochondrial mass and number, but accumulated depolarized mitochondria, correlating with reduced clonogenicity.
- Dexamethasone-treated 2B4 T-cells exhibited decreased Δψm without mitochondrial proliferation.
- Cycloheximide and Bcl-2 inhibited mitochondrial proliferation and/or Δψm loss, preventing cell death in respective models.
Conclusions:
- Apoptotic cell death involves diverse mitochondrial responses depending on the cellular context.
- Cell death is linked to a decreased ratio of mitochondrial potential to mitochondrial mass, suggesting accumulation of dysfunctional mitochondria.