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Swelling of free-radical-induced megamitochondria causes apoptosis

M Teranishi1, J H Spodonik, M Karbowski

  • 1Department of Cell Biology and Molecular Pathology, Nagoya University School of Medicine, Nagoya, 466-8550, Japan.

Experimental and Molecular Pathology
|March 16, 2000
PubMed

Insights

Megamitochondria (MG), enlarged mitochondria, are linked to cellular apoptosis. This study found that MG, including enlarged and normal-sized mitochondria, contributes to cell death, with secondary swelling of MG triggering apoptotic changes.

Area of Science:

  • Cell Biology
  • Mitochondrial Research
  • Apoptosis

Background:

  • Cultured cells exposed to free radicals undergo apoptosis in the presence of megamitochondria (MG).
  • The composition and function of MG, particularly its role in apoptosis, require further investigation.

Purpose of the Study:

  • To determine if the "MG fraction," containing enlarged and normal-sized mitochondria, reflects MG functions.
  • To elucidate the correlation between megamitochondria formation and cellular apoptotic changes.

Main Methods:

  • Isolation of heavy (enlarged mitochondria) and light (normal-sized mitochondria) fractions from rat livers after 4 and 8 days of hydrazine treatment.
  • Comparison of apoptosis-related functions, including mitochondrial swelling, membrane potential, and reactive oxygen species generation, between fractions and controls.

Main Results:

  • Mitochondria from 8H animals showed reduced swelling, indicating pre-opened permeability transition pores.
  • Mitochondrial membrane potential was significantly decreased in both fractions from 8H animals.
  • Reactive oxygen species generation was elevated in 4H animals but decreased in 8H animals, with no difference between fractions.

Conclusions:

  • Enlarged and normal-sized mitochondria constitute megamitochondria (MG).
  • Secondary swelling of MG is the cause of apoptotic changes in cells.
  • These findings clarify the role of MG in cellular apoptosis.

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