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 586-97
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 14.248
Times Cited 78
C.elegans tm1133 tm1107 tm1108 tm1867 tm2227 tm1832 tm1867