RRC ID 46157
Author Lu Y, Rolland SG, Conradt B.
Title A molecular switch that governs mitochondrial fusion and fission mediated by the BCL2-like protein CED-9 of Caenorhabditis elegans.
Journal Proc Natl Acad Sci U S A
Abstract Depending on the cellular context, BCL2-like proteins promote mitochondrial fusion or fission. What determines which of these two opposing processes they promote has so far been unknown. Furthermore, the mechanisms through which BCL2-like proteins affect mitochondrial dynamics remain to be fully understood. The BCL2-like protein CED-9 of Caenorhabditis elegans has previously been shown to promote mitochondrial fusion by physically interacting with the mitochondrial fusion protein FZO-1. Here, we report that CED-9 also physically interacts with the mitochondrial fission protein DRP-1 and that this interaction can be enhanced when CED-9 is associated with the BH3-only protein EGL-1. In addition, we show that the EGL-1-CED-9 complex promotes mitochondrial fission by recruiting DRP-1 to mitochondria and that the egl-1 gene is required for CED-9-dependent mitochondrial fission in vivo. Based on these results, we propose that EGL-1 converts CED-9 into a mitochondrial receptor for DRP-1, thereby shifting its activity from profusion to profission. We hypothesize that BCL2-like proteins act as mitochondrial receptors for DRP-1-like proteins in higher organisms as well and that BH3-only proteins play a general role as modifiers of the function in mitochondrial dynamics of BCL2-like proteins. We speculate that this function of BCL2-like proteins may be as couplers of mitochondrial fusion and fission.
Volume 108(41)
Pages E813-22
Published 2011-10-11
DOI 10.1073/pnas.1103218108
PII 1103218108
PMID 21949250
PMC PMC3193245
MeSH Animals Animals, Genetically Modified Caenorhabditis elegans / genetics Caenorhabditis elegans / metabolism* Caenorhabditis elegans / ultrastructure Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* Calcium-Binding Proteins / genetics Calcium-Binding Proteins / metabolism Dynamins / genetics Dynamins / metabolism GTP Phosphohydrolases / genetics GTP Phosphohydrolases / metabolism Guanosine Triphosphate / metabolism Mitochondria / metabolism* Mitochondria / ultrastructure Models, Biological Multiprotein Complexes / metabolism Proto-Oncogene Proteins c-bcl-2 / genetics Proto-Oncogene Proteins c-bcl-2 / metabolism* Repressor Proteins / genetics Repressor Proteins / metabolism
IF 9.58
Times Cited 28
C.elegans tm1108