Publication Date:
2002-08-24
Description:
A current view is that cytotoxic stress, such as DNA damage, induces apoptosis by regulating the permeability of mitochondria. Mitochondria sequester several proteins that, if released, kill by activating caspases, the proteases that disassemble the cell. Cytokines activate caspases in a different way, by assembling receptor complexes that activate caspases directly; in this case, the subsequent mitochondrial permeabilization accelerates cell disassembly by amplifying caspase activity. We found that cytotoxic stress causes activation of caspase-2, and that this caspase is required for the permeabilization of mitochondria. Therefore, we argue that cytokine-induced and stress-induced apoptosis act through conceptually similar pathways in which mitochondria are amplifiers of caspase activity rather than initiators of caspase activation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lassus, Patrice -- Opitz-Araya, Ximena -- Lazebnik, Yuri -- CA-13106-31/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2002 Aug 23;297(5585):1352-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12193789" target="_blank"〉PubMed〈/a〉
Keywords:
*Apoptosis
;
Apoptotic Protease-Activating Factor 1
;
Caspase 2
;
Caspases/genetics/*metabolism
;
Cell Line, Transformed
;
Cytochrome c Group/metabolism
;
*DNA Damage
;
Enzyme Activation
;
Enzyme Repression
;
Etoposide/pharmacology
;
Humans
;
Mitochondria/metabolism/*physiology
;
Permeability
;
Protein Transport
;
Proteins/genetics/metabolism
;
Proto-Oncogene Proteins/metabolism
;
*Proto-Oncogene Proteins c-bcl-2
;
RNA, Small Interfering
;
RNA, Untranslated
;
Signal Transduction
;
Transfection
;
Tumor Cells, Cultured
;
Tumor Necrosis Factor-alpha/pharmacology
;
bcl-2-Associated X Protein
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
