Alternative Germ Cell Death Pathway in Drosophila Involves HtrA2/Omi, Lysosomes, and a Caspase-9 Counterpart
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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.
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A type of RCD highly reminiscent of lysosome-dependent cell death, dubbed germ cell death, appears to play a critical role in physiological elimination of a fraction of emerging male germ cells at least in D. melanogaster.
“a type of RCD that is highly reminiscent of lysosome-dependent cell death, which has been dubbed “germ cell death”, appears to play a critical role in the physiological elimination of a fraction of emerging male germ cells (at least in D. melanogaster) [753–756].”
From Molecular mechanisms of cell death: recommendations of the nomenclature committee on cell death 2018. (2018) · cites this paper as [753]
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Live to die another way: modes of programmed cell death and the signals emanating from dying cells
Interdisciplinary, L. L. (2015)
- Authors
- Yacobi-Sharon, K., Namdar, Y., & Arama, E.
- Affiliations
- Weizmann Institute of Science (IL)
- Corresponding author
- Arama, Eli
- Venue
- Developmental Cell
- Publisher
- Elsevier BV
- Published
- 2013-04
- Volume
- 25
- Issue
- 1
- Pages
- 29-42
- ISSN
- 1534-5807 (ISSN-L)
- OpenAlex
- W1999588722
- Cited by
- 119
- References
- 74
- Citations by year
- 2026: 7 · 2025: 8 · 2024: 10 · 2023: 16 · 2022: 6 · 2021: 5 · 2020: 5 · 2019: 6 · 2018: 14 · 2017: 8 · 2016: 8 · 2015: 16 · 2014: 6 · 2013: 4
- FWCI
- 5.07
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Developmental Cell (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Minerva Foundation
- Bundesministerium für Bildung und Forschung
- Fritz Thyssen Stiftung
- Israel Cancer Association
- Israel Science Foundation (308/09)
- Israel Cancer Research Fund
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Keywords
- germ cell death, Drosophila, Omi/HtrA2, lysosomes, caspase-9, Dronc, apoptosis, necrosis, PINK1, endonuclease G, mitochondrial protease, Parkinson's disease, male germ cells, developmental cell death
- MeSH terms
- High-Temperature Requirement A Serine Peptidase 2, PTEN-Induced Putative Kinase, Animals, Cell Division, Drosophila, Enzyme Activation, Germ Cells, Lysosomes, Male, Mitochondria, Serine Endopeptidases, Species Specificity, Spermatogenesis, Spermatozoa, Testis, Cell Death, Protein Serine-Threonine Kinases, Reactive Oxygen Species, Caspases, In Situ Nick-End Labeling, Drosophila Proteins, Microscopy, Electron, Transmission, Caspase 9, DNA Fragmentation
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