Mitochondrial aggregation precedes cytochrome c release from mitochondria during apoptosis

Mitochondria play a central role in apoptotic signaling pathways. Upon exposure to apoptotic stimuli, mitochondria release cytochrome c to the cytoplasm and activate caspase cascade leading to cell death. However, the events upstream of cytochrome c release are not fully understood. Here, we quantit...

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Bibliographic Details
Published inOncogene Vol. 22; no. 36; pp. 5579 - 5585
Main Authors HAGA, Naomi, FUJITA, Naoya, TSURUO, Takashi
Format Journal Article
LanguageEnglish
Published Basingstoke Nature Publishing 28.08.2003
Nature Publishing Group
Subjects
Ageing, cell death
Animals
Apoptosis
Apoptosis - drug effects
Bcl-x protein
Biological and medical sciences
Caspase 3
Caspases - physiology
Cell death
Cell Line
Cell physiology
COS Cells
Cytochrome
Cytochrome c
Cytochrome c Group - secretion
Cytometry
Cytoplasm
Etoposide - pharmacology
Fundamental and applied biological sciences. Psychology
Humans
Localization
Mitochondria
Mitochondria - physiology
Molecular and cellular biology
Morphology
Signal transduction
Transfection
Japan
Aggregation
Cytochrome c
Mitochondria
laser scanning cytometer
Release
Apoptosis
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Summary:Mitochondria play a central role in apoptotic signaling pathways. Upon exposure to apoptotic stimuli, mitochondria release cytochrome c to the cytoplasm and activate caspase cascade leading to cell death. However, the events upstream of cytochrome c release are not fully understood. Here, we quantitate mitochondrial aggregation in situ using a novel laser scanning cytometry technique and reveal that mitochondria aggregate during apoptosis in a budding-like shape. The quantitative analysis reveals that mitochondrial aggregation is not inhibited by caspase-3 inhibitor ZEVD. Furthermore, bcl-x(L) transfection cannot suppress mitochondrial aggregation. However, overexpression of bcl-x(L) inhibits cytochrome c release from mitochondria. Therefore, mitochondrial aggregation is an event upstream of cytochrome c release during apoptosis. This mitochondrial aggregation was not observed in human leukemia H9 cells where apoptosis occurs in a mitochondria-independent fashion. Our studies imply that changes in the localization of mitochondria participate in the regulation of apoptosis through cytochrome c release.
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ISSN:0950-9232
1476-5594
DOI:10.1038/sj.onc.1206576