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PMID:23523076

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Citation

Yacobi-Sharon, K, Namdar, Y and Arama, E (2013) Alternative germ cell death pathway in Drosophila involves HtrA2/Omi, lysosomes, and a caspase-9 counterpart. Dev. Cell 25:29-42

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.

Links

PubMed Online version:10.1016/j.devcel.2013.02.002

Keywords

Animals; Caspase 9/genetics; Caspase 9/metabolism; Caspases/genetics; Caspases/metabolism; Cell Death; Cell Division; DNA Fragmentation; Drosophila/enzymology; Drosophila/genetics; Drosophila/metabolism; Drosophila Proteins/genetics; Drosophila Proteins/metabolism; Enzyme Activation; Germ Cells/metabolism; Germ Cells/ultrastructure; In Situ Nick-End Labeling; Lysosomes/genetics; Lysosomes/metabolism; Male; Microscopy, Electron, Transmission; Mitochondria/enzymology; Mitochondria/genetics; Mitochondria/metabolism; Protein-Serine-Threonine Kinases/genetics; Protein-Serine-Threonine Kinases/metabolism; Reactive Oxygen Species/metabolism; Serine Endopeptidases/genetics; Serine Endopeptidases/metabolism; Species Specificity; Spermatogenesis; Spermatozoa/metabolism; Spermatozoa/ultrastructure; Testis/cytology; Testis/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

DROME:PINK1

involved_in

GO:0035234: ectopic germ cell programmed cell death

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:Q7JXB9

involved_in

GO:0035234: ectopic germ cell programmed cell death

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:Q7KJ42

involved_in

GO:0035234: ectopic germ cell programmed cell death

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:Q7KM33

involved_in

GO:0035234: ectopic germ cell programmed cell death

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:Q8T8Y5

involved_in

GO:0035234: ectopic germ cell programmed cell death

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:Q95U83

involved_in

GO:0035234: ectopic germ cell programmed cell death

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:Q9NGX3

involved_in

GO:0035234: ectopic germ cell programmed cell death

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:Q9V9C8

involved_in

GO:0035234: ectopic germ cell programmed cell death

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:HTRA2

involved_in

GO:0035234: ectopic germ cell programmed cell death

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:DRONC

involved_in

GO:0035234: ectopic germ cell programmed cell death

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:Q961J3

involved_in

GO:0035234: ectopic germ cell programmed cell death

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:Q0KHV6

involved_in

GO:0035234: ectopic germ cell programmed cell death

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:ICENC

involved_in

GO:0035234: ectopic germ cell programmed cell death

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

Notes

See also

References

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