Caenorhabditis elegans drp-1 and fis-2 regulate distinct cell-death execution pathways downstream of ced-3 and independent of ced-9.
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.
Breckenridge
David G
DG
Department of Molecular, Cellular and Developmental Biology, University of Colorado, Boulder, CO 80309, USA.
Kang
Byung-Ho
BH
Department of Molecular, Cellular and Developmental Biology, University of Colorado, Boulder, CO 80309, USA; Department of Microbiology and Cell Science, Integrated Center for Biotechnology Research, University of Florida, Gainesville, FL 32608, USA.
Kokel
David
D
Department of Molecular, Cellular and Developmental Biology, University of Colorado, Boulder, CO 80309, USA.
Mitani
Shohei
S
Department of Physiology, Tokyo Women's Medical University, School of Medicine, and CREST, JST, Tokyo, 162-8666, Japan.
Staehelin
L Andrew
LA
Department of Molecular, Cellular and Developmental Biology, University of Colorado, Boulder, CO 80309, USA.
Xue
Ding
D
Department of Molecular, Cellular and Developmental Biology, University of Colorado, Boulder, CO 80309, USA. Electronic address: ding.xue@colorado.edu.
D000818:Animals; D017173:Caenorhabditis elegans / Q000166:cytology* / Q000648:ultrastructure; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism*; D020169:Caspases / Q000378:metabolism*; D016923:Cell Death; D002470:Cell Survival; D018509:DNA, Helminth / Q000378:metabolism; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000648:ultrastructure; D008928:Mitochondria / Q000648:ultrastructure; D009154:Mutation / Q000235:genetics; D010614:Pharynx / Q000166:cytology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism
D029742:Caenorhabditis elegans Proteins; C087233:Ced-9 protein, C elegans; D018509:DNA, Helminth; D019253:Proto-Oncogene Proteins c-bcl-2; D020169:Caspases; C089223:ced-3 protein, C elegans