Hsp60D is essential for caspase-mediated induced apoptosis in Drosophila melanogaster

Cell Stress Chaperones. 2008 Dec;13(4):509-26. doi: 10.1007/s12192-008-0051-3. Epub 2008 May 28.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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
  • ErbB Receptors / metabolism
  • 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
  • Receptors, Invertebrate Peptide / metabolism


  • Chaperonin 60
  • DIAP1 protein, Drosophila
  • Drosophila Proteins
  • Hsp60D protein, Drosophila
  • Inhibitor of Apoptosis Proteins
  • RNA, Messenger
  • Receptors, Invertebrate Peptide
  • Egfr protein, Drosophila
  • ErbB Receptors
  • JNK Mitogen-Activated Protein Kinases
  • Galactosidases
  • Caspases
  • dronc protein, Drosophila