Article: C. elegans mitochondrial factor WAH-1 promotes phosphatidylserine externalization in apoptotic cells through phospholipid scramblase SCRM-1.
2007 Volume 9, Issue 5, Page(s) 541–549
Abstract: ... apoptosis-inducing factor (AIF) homologue (WAH-1), a mitochondrial apoptogenic factor, or the C. elegans ... of apoptotic germ cells and compromises cell-corpse engulfment. WAH-1 associates with SCRM-1 and activates ... its phospholipid scrambling activity in vitro. Thus WAH-1, after its release from mitochondria during apoptosis ...
| Abstract | Externalization of phosphatidylserine, which is normally restricted to the inner leaflet of plasma membrane, is a hallmark of mammalian apoptosis. It is not known what activates and mediates the phosphatidylserine externalization process in apoptotic cells. Here, we report the development of an annexin V-based phosphatidylserine labelling method and show that a majority of apoptotic germ cells in Caenorhabditis elegans have surface-exposed phosphatidylserine, indicating that phosphatidylserine externalization is a conserved apoptotic event in worms. Importantly, inactivation of the gene encoding either the C. elegans apoptosis-inducing factor (AIF) homologue (WAH-1), a mitochondrial apoptogenic factor, or the C. elegans phospholipid scramblase 1 (SCRM-1), a plasma membrane protein, reduces phosphatidylserine exposure on the surface of apoptotic germ cells and compromises cell-corpse engulfment. WAH-1 associates with SCRM-1 and activates its phospholipid scrambling activity in vitro. Thus WAH-1, after its release from mitochondria during apoptosis, promotes plasma membrane phosphatidylserine externalization through its downstream effector, SCRM-1. |
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| MeSH term(s) | Animals ; Annexin A5/metabolism ; Apoptosis ; Biological Transport ; Caenorhabditis elegans/cytology ; Caenorhabditis elegans/enzymology ; Caenorhabditis elegans/metabolism ; Caenorhabditis elegans Proteins/genetics ; Caenorhabditis elegans Proteins/metabolism ; Caspases/genetics ; Caspases/metabolism ; Cell Membrane/metabolism ; Germ Cells/enzymology ; Germ Cells/metabolism ; Membrane Proteins/genetics ; Membrane Proteins/metabolism ; Mitochondria/metabolism ; Mitochondrial Proteins/genetics ; Mitochondrial Proteins/metabolism ; Models, Molecular ; Mutation ; Phosphatidylserines/metabolism ; Phospholipid Transfer Proteins/genetics ; Phospholipid Transfer Proteins/metabolism ; RNA Interference ; Staining and Labeling/methods ; Time Factors |
| Chemical Substances | Annexin A5 ; CED-2 protein, C elegans ; Caenorhabditis elegans Proteins ; Membrane Proteins ; Mitochondrial Proteins ; Phosphatidylserines ; Phospholipid Transfer Proteins ; SCRM-1 protein, C elegans ; Wah-1 protein, C elegans ; ced-1 protein, C elegans ; Caspases (EC 3.4.22.-) ; ced-3 protein, C elegans (EC 3.4.22.-) |
| Language | English |
| Publishing date | 2007-05 |
| Publishing country | England |
| Document type | Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't |
| ZDB-ID | 1474722-4 |
| ISSN | 1476-4679 ; 1465-7392 |
| ISSN (online) | 1476-4679 |
| ISSN | 1465-7392 |
| DOI | 10.1038/ncb1574 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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