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Temporal relationship between cytochrome c release and mitochondrial swelling during UV-induced apoptosis in living HeLa cells

Authors Gao, WH
Pu, YM
Luo, KQ
Chang, DC
Issue Date 2001
Source Journal of cell science , v. 114, (15), 2001, AUG, p. 2855-2862
Summary During apoptosis, cytochrome c is released from mitochondria to the cytosol to activate a caspase cascade, which commits the cell to the death process. It has been proposed that the release of cytochrome c is caused by a swelling of the mitochondrial matrix triggered by the apoptotic stimuli. To test this theory, we measured directly the dynamic re-distribution of green fluorescence protein (GFP)-tagged cytochrome c and morphological change of mitochondria within living HeLa cells during u.v.-induced apoptosis. We observed that mitochondria did not swell when cytochrome c was released from mitochondria to cytosol during apoptosis. Instead, mitochondria swelled to spherical shapes within 10 minutes of cytochrome c release. This finding strongly suggests that cytochrome c release in apoptosis was not caused by mitochondrial swelling. This conclusion was further supported in two separated experiments using an immunostaining method and carbonyl cyanide m-chlorophenyl-hydrazone (CCCP) treatment. In addition, we found evidence that cytochrome c was also released before mitochondrial swelling in apoptosis induced by other cell death-inducing treatments, including tumor necrosis factor (TNF) and actinomycin D.
ISSN 0021-9533
Rights Permission is granted by the Company of Biologists Ltd. The paper was published in J Cell Sci 2001 114 : 2855-2862.
Language English
Format Article
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