title: Alternative germ cell death pathway in Drosophila involves HtrA2/Omi, lysosomes, and a caspase-9 counterpart.
abstract: In both flies and mammals, almost one-third of the newly emerging male germ cells are spontaneously eliminated before entering meiosis. Here, we show that in Drosophila, germ cell death (GCD) involves the initiator caspase Dronc independently of the apoptosome and the main executioner caspases. Electron microscopy of dying germ cells revealed mixed morphologies of apoptosis and necrosis. We further show that the lysosomes and their catabolic enzymes, but not macroautophagy, are involved in the execution of GCD. We then identified, in a screen, the Parkinson's disease-associated mitochondrial protease, HtrA2/Omi, as an important mediator of GCD, acting mainly through its catalytic activity rather than by antagonizing inhibitor of apoptosis proteins. Concomitantly, other mitochondrial-associated factors were also implicated in GCD, including Pink1 (but not Parkin), the Bcl-2-related proteins, and endonuclease G, which establish the mitochondria as central mediators of GCD. These findings uncover an alternative developmental cell death pathway in metazoans.
authors.affiliation: Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Keren
authors.initials: K
authors.lastname: Yacobi-Sharon
authors.forename: Yuval
authors.initials: Y
authors.lastname: Namdar
authors.forename: Eli
authors.initials: E
authors.lastname: Arama
mesh_terms: D000818:Animals; D053453:Caspase 9 / Q000235:genetics / Q000378:metabolism*; D020169:Caspases / Q000235:genetics / Q000378:metabolism*; D016923:Cell Death; D002455:Cell Division; D053938:DNA Fragmentation; D004330:Drosophila / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004789:Enzyme Activation; D005854:Germ Cells / Q000378:metabolism / Q000648:ultrastructure*; D000074923:High-Temperature Requirement A Serine Peptidase 2; D020287:In Situ Nick-End Labeling; D008247:Lysosomes / Q000235:genetics / Q000378:metabolism*; D008297:Male; D046529:Microscopy, Electron, Transmission; D008928:Mitochondria / Q000201:enzymology / Q000235:genetics / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D012697:Serine Endopeptidases / Q000235:genetics / Q000378:metabolism*; D013045:Species Specificity; D013091:Spermatogenesis; D013094:Spermatozoa / Q000378:metabolism / Q000648:ultrastructure*; D013737:Testis / Q000166:cytology / Q000378:metabolism; D000099202:PTEN-Induced Putative Kinase
chemical_list: D053453:Caspase 9; D020169:Caspases; D029721:Drosophila Proteins; D000074923:High-Temperature Requirement A Serine Peptidase 2; D017346:Protein Serine-Threonine Kinases; D017382:Reactive Oxygen Species; D012697:Serine Endopeptidases; C534484:PINK1 protein, Drosophila; D000099202:PTEN-Induced Putative Kinase; C530280:HtrA2 protein, Drosophila; C118731:dronc protein, Drosophila