Swelling of free-radical-induced megamitochondria causes apoptosis.
Recently, we have found that cultured cells from various sources exposed to free radicals become apoptotic in the presence of megamitochondria (MG). The purpose of the present study is to answer the following two questions: (1) Do functions obtained from the "MG fraction" isolated from normal mitochondria by a routine procedure represent the functions of MG since the fraction consists of enlarged and normal-size mitochondria? (2) What is the correlation between MG formation and apoptotic changes of the cell? In the present study the heavy fraction rich in mitochondria enlarged to varying degrees and the light fraction consisting mainly of normal-size mitochondria were isolated independently from the livers of rats treated with hydrazine for 4 days (4H animals) and 8 days (8H animals), and some functions related to apoptosis were compared. Results were as follows: (1) Mitochondria in both fractions obtained from 8H animals swelled far less in various media than those obtained from the controls, suggesting that the permeability transition pores had been opened before they were exposed to swelling media. (2) The membrane potential of mitochondria in both fractions obtained from 8H animals was distinctly decreased. (3) The rates of reactive oxygen species generation from mitochondria of both fractions in 4H animals were equally elevated, while those in 8H animals were equally decreased compared to those of controls. These results, together with morphological data obtained in the present study, suggest that enlarged and normal-size mitochondria are a part of MG and that the secondary swelling of MG causes the apoptotic changes in the cell.
Teranishi
M
M
Department of Cell Biology and Molecular Pathology, Nagoya University School of Medicine, Nagoya, 466-8550, Japan.
Spodonik
J H
JH
Karbowski
M
M
Kurono
C
C
Soji
T
T
Wakabayashi
T
T
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D002478:Cells, Cultured; D002701:Chloramphenicol / Q000494:pharmacology; D003580:Cytochromes / Q000378:metabolism; D005434:Flow Cytometry; D005609:Free Radicals / Q000378:metabolism; D006834:Hydrazines / Q000494:pharmacology; D008099:Liver / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008564:Membrane Potentials; D051379:Mice; D008854:Microscopy, Electron; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure*; D008933:Mitochondrial Swelling; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism
D003580:Cytochromes; D005609:Free Radicals; D006834:Hydrazines; D017382:Reactive Oxygen Species; C029424:hydrazine; D002701:Chloramphenicol