| RRC ID |
4325
|
| Author |
Breckenridge DG, Kang BH, Kokel D, Mitani S, Staehelin LA, Xue D.
|
| Title |
Caenorhabditis elegans drp-1 and fis-2 regulate distinct cell-death execution pathways downstream of ced-3 and independent of ced-9.
|
| Journal |
Mol Cell
|
| Abstract |
The dynamin family of GTPases regulate mitochondrial fission and fusion processes and have been implicated in controlling the release of caspase activators from mitochondria during apoptosis. Here we report that profusion genes fzo-1 and eat-3 or the profission gene drp-1 are not required for apoptosis activation in C. elegans. However, minor proapoptotic roles for drp-1 and fis-2, a homolog of human Fis1, are revealed in sensitized genetic backgrounds. drp-1 and fis-2 function independent of one another and the Bcl-2 homolog CED-9 and downstream of the CED-3 caspase to promote elimination of mitochondria in dying cells, an event that could facilitate cell-death execution. Interestingly, CED-3 can cleave DRP-1, which appears to be important for DRP-1's proapoptotic function, but not its mitochondria fission function. Our findings demonstrate that mitochondria dynamics do not regulate apoptosis activation in C. elegans and reveal distinct roles for drp-1 and fis-2 as mediators of cell-death execution downstream of caspase activation.
|
| Volume |
31(4)
|
| Pages |
586-597
|
| Published |
2008-8-22
|
| DOI |
10.1016/j.molcel.2008.07.015
|
| PII |
S1097-2765(08)00504-2
|
| PMID |
18722182
|
| PMC |
PMC2548325
|
| MeSH |
Animals
Caenorhabditis elegans / cytology*
Caenorhabditis elegans / ultrastructure
Caenorhabditis elegans Proteins / metabolism*
Caspases / metabolism*
Cell Death
Cell Survival
DNA, Helminth / metabolism
Embryo, Nonmammalian / cytology
Embryo, Nonmammalian / ultrastructure
Mitochondria / ultrastructure
Mutation / genetics
Pharynx / cytology
Proto-Oncogene Proteins c-bcl-2 / metabolism
|
| IF |
15.584
|
| Times Cited |
94
|
|
WOS Category
|
BIOCHEMISTRY & MOLECULAR BIOLOGY
CELL BIOLOGY
|
| Resource |
| C.elegans |
tm1133
tm1107
tm1108
tm1867
tm2227
tm1832
tm1867 |
