Mitochondrial disruption in Drosophila apoptosis.
Mitochondrial disruption is a conserved aspect of apoptosis, seen in many species from mammals to nematodes. Despite significant conservation of other elements of the apoptotic pathway in Drosophila, a broad role for mitochondrial changes in apoptosis in flies remains unconfirmed. Here, we show that Drosophila mitochondria become permeable in response to the expression of Reaper and Hid, endogenous regulators of developmental apoptosis. Caspase activation in the absence of Reaper and Hid is not sufficient to permeabilize mitochondria, but caspases play a role in Reaper- and Hid-induced mitochondrial changes. Reaper and Hid rapidly localize to mitochondria, resulting in changes in mitochondrial ultrastructure. The dynamin-related protein, Drp1, is important for Reaper- and DNA-damage-induced mitochondrial disruption. Significantly, we show that inhibition of Reaper or Hid mitochondrial localization or inhibition of Drp1 significantly inhibits apoptosis, indicating a role for mitochondrial disruption in fly apoptosis.
Abdelwahid
Eltyeb
E
Cutaneous Biology Research Center, Massachusetts General Hospital/Harvard Medical School, Building 149, 13th Street, Charlestown, MA 02129, USA.
Yokokura
Takakazu
T
Krieser
Ronald J
RJ
Balasundaram
Sujatha
S
Fowle
William H
WH
White
Kristin
K
D000818:Animals; D017209:Apoptosis / Q000528:radiation effects; D020169:Caspases / Q000378:metabolism; D045304:Cytochromes c / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000378:metabolism; D029721:Drosophila Proteins / Q000737:chemistry / Q000378:metabolism; D004331:Drosophila melanogaster / Q000166:cytology* / Q000201:enzymology / Q000528:radiation effects / Q000648:ultrastructure; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000378:metabolism / Q000528:radiation effects; D004789:Enzyme Activation / Q000528:radiation effects; D019204:GTP-Binding Proteins / Q000378:metabolism; D008928:Mitochondria / Q000201:enzymology / Q000378:metabolism* / Q000528:radiation effects / Q000648:ultrastructure; D051336:Mitochondrial Membranes / Q000378:metabolism; D050505:Mutant Proteins / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D009479:Neuropeptides / Q000737:chemistry / Q000378:metabolism; D010539:Permeability / Q000528:radiation effects; D017434:Protein Structure, Tertiary; D021381:Protein Transport / Q000528:radiation effects; D011839:Radiation, Ionizing
D003598:Cytoskeletal Proteins; D029721:Drosophila Proteins; C108880:HID protein, Drosophila; D050505:Mutant Proteins; D009479:Neuropeptides; C086973:rpr protein, Drosophila; D045304:Cytochromes c; D020169:Caspases; C504426:DRP1 protein, Drosophila; D019204:GTP-Binding Proteins