期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 103, 期 31, 页码 11573-11578出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0603007103
关键词
apoptosis-inducing factor; cytochrome c; mitochondria; Omi; Smac
资金
- NCI NIH HHS [P01 CA069381, CA69381] Funding Source: Medline
- NIAID NIH HHS [AI52735, AI40646, R01 AI040646] Funding Source: Medline
The release of mitochondrial intermembrane space proteins to the cytosol is a key event during apoptosis. We used in situ fluorescent labeling of proteins tagged with a short tetracysteine-containing sequence to follow the release of Smac, Omi, adenylate kinase-2, cytochrome c, and apoptosis-inducing factor (AIF) during apoptosis and compared the release with that of cytochrome c tagged with GFP in individual cells observed overtime. We observed a caspase-independent, simultaneous release of cytochrome c, Smac, Omi, and adenylate kinase-2. Although AIF release also was caspase-independent and commenced with that of the other proteins, it proceeded much more slowly and incompletely from mitochondria, perhaps because of a requirement for a secondary event. These results suggest that these proteins are released through the same mitochondrial pore and that apoptosis may not be regulated through a selective release of individual mitochondrial proteins. The timing and extent of AIF release makes it unlikely that it is involved in the induction of apoptosis, either upstream or downstream of mitochondrial outer membrane permeabilization.
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