RRC ID 11113
Author Arya R, Lakhotia SC.
Title Hsp60D is essential for caspase-mediated induced apoptosis in Drosophila melanogaster.
Journal Cell Stress Chaperones
Abstract Apart from their roles as chaperones, heat shock proteins are involved in other vital activities including apoptosis with mammalian Hsp60 being ascribed proapoptotic as well as antiapoptotic roles. Using conditional RNAi or overexpression of Hsp60D, a member of the Hsp60 family in Drosophila melanogaster, we show that the downregulation of this protein blocks caspase-dependent induced apoptosis. GMR-Gal4-driven RNAi for Hsp60D in developing eyes dominantly suppressed cell death caused by expression of Reaper, Hid, or Grim (RHG), the key activators of canonical cell death pathway. Likewise, Hsp60D-RNAi rescued cell death induced by GMR-Gal4-directed expression of full-length and activated DRONC. Overexpression of Hsp60D enhanced cell death induced either by directed expression of RHG or DRONC. However, the downregulation of Hsp60D failed to suppress apoptosis caused by unguarded caspases in DIAP1-RNAi flies. Furthermore, in DIAP1-RNAi background, Hsp60D-RNAi also failed to inhibit apoptosis induced by RHG expression. The Hsp60 and DIAP1 show diffuse and distinct granular overlapping distributions in the photoreceptor cells with the bulk of both proteins being outside the mitochondria. Depletion of either of these proteins disrupts the granular distribution of the other. We suggest that in the absence of Hsp60D, DIAP1 is unable to dissociate from effecter and executioner caspases, which thus remain inactive.
Volume 13(4)
Pages 509-26
Published 2008-12
DOI 10.1007/s12192-008-0051-3
PMID 18506601
PMC PMC2673934
MeSH Animals Animals, Genetically Modified Apoptosis* Caspases / metabolism* Chaperonin 60 / genetics Chaperonin 60 / metabolism* Cytoplasmic Granules / metabolism Down-Regulation Drosophila Proteins / genetics Drosophila Proteins / metabolism* Drosophila melanogaster / cytology* Drosophila melanogaster / embryology Drosophila melanogaster / enzymology* Embryonic Development Eye / cytology Eye / enzymology Galactosidases / metabolism Gene Expression Regulation, Developmental Homozygote Inhibitor of Apoptosis Proteins / metabolism JNK Mitogen-Activated Protein Kinases / metabolism Larva / metabolism Mitochondria / metabolism Mutation / genetics Phenotype Photoreceptor Cells, Invertebrate / cytology Photoreceptor Cells, Invertebrate / metabolism RNA Interference RNA, Messenger / genetics RNA, Messenger / metabolism Receptor, Epidermal Growth Factor / metabolism Receptors, Invertebrate Peptide / metabolism
IF 2.571
Times Cited 10