Open AccessDifferent mitochondrial intermembrane space proteins are released during apoptosis in a manner that is coordinately initiated but can vary in duration
Author(s) -
Cristina Muñoz-Pinedo,
Ana Guío-Carrión,
Joshua C. Goldstein,
Patrick Fitzgerald,
Donald D. Newmeyer,
Douglas R. Green
Publication year - 2006
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.0603007103
Subject(s) - mitochondrial intermembrane space , intermembrane space , cytochrome c , microbiology and biotechnology , apoptosis inducing factor , mitochondrial apoptosis induced channel , mitochondrion , biology , apoptosis , adenylate kinase , inner mitochondrial membrane , cytosol , biochemistry , caspase , programmed cell death , bacterial outer membrane , gene , enzyme , escherichia coli
The release of mitochondrial intermembrane space proteins to the cytosol is a key event during apoptosis. We usedin situ fluorescent labeling of proteins tagged with a short tetracysteine-containing sequence to follow the release of Smac, Omi, adenylate kinase-2, cytochromec , and apoptosis-inducing factor (AIF) during apoptosis and compared the release with that of cytochromec tagged with GFP in individual cells observed over time. We observed a caspase-independent, simultaneous release of cytochromec , 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.