Suppression of CED-3-independent apoptosis by mitochondrial betaNAC in Caenorhabditis elegans.

TitleSuppression of CED-3-independent apoptosis by mitochondrial betaNAC in Caenorhabditis elegans.
Publication TypeJournal Article
Year of Publication2003
AuthorsBloss TA, Witze ES, Rothman JH
JournalNature
Volume424
Issue6952
Pagination1066-71
Date Published2003 Aug 28
ISSN1476-4687
KeywordsAmino Acid Sequence, Animals, Apoptosis, Apoptosis Regulatory Proteins, Caenorhabditis elegans, Caenorhabditis elegans Proteins, Calcium-Binding Proteins, Caspases, Heat-Shock Response, Intestines, Mitochondria, Molecular Chaperones, Molecular Sequence Data, Mutation, Neurons, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-bcl-2, RNA Interference, Trans-Activators
Abstract

To ensure cell survival, it is essential that the ubiquitous pro-apoptotic machinery is kept quiescent. As death is irreversible, cells must continually integrate developmental information with regulatory inputs to control the switch between repressing and activating apoptosis. Inappropriate activation or suppression of apoptosis can lead to degenerative pathologies or tumorigenesis, respectively. Here we report that Caenorhabditis elegans inhibitor of cell death-1 (ICD-1) is necessary and sufficient to prevent apoptosis. Loss of ICD-1 leads to inappropriate apoptosis in developing and differentiated cells in various tissues. Although this apoptosis requires CED-4, it occurs independently of CED-3--the caspase essential for developmental apoptosis--showing that these core pro-apoptotic proteins have separable roles. Overexpressing ICD-1 inhibits the apoptosis of cells that are normally programmed to die. ICD-1 is the beta-subunit of the nascent polypeptide-associated complex (betaNAC) and contains a putative caspase-cleavage site and caspase recruitment domain. It localizes primarily to mitochondria, underscoring the role of mitochondria in coordinating apoptosis. Human betaNAC is a caspase substrate that is rapidly eliminated in dying cells, suggesting that ICD-1 apoptosis-suppressing activity may be inactivated by caspases.

DOI10.1038/nature01920
Alternate JournalNature
PubMed ID12944970