Evolution of mitochondrial cell death pathway: Proapoptotic role of HtrA2/Omi in Drosophila

Despite the essential role of mitochondria in a variety of mammalian cell death processes, the involvement of mitochondrial pathway in Drosophila cell death has remained unclear. To address this, we cloned and characterized DmHtrA2, a Drosophila homolog of a mitochondrial serine protease HtrA2/Omi....

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Bibliographic Details
Published in:Biochemical and biophysical research communications 2007-05, Vol.356 (4), p.993-997
Main Authors: Igaki, Tatsushi, Suzuki, Yasuyuki, Tokushige, Naoko, Aonuma, Hiroka, Takahashi, Ryosuke, Miura, Masayuki
Format: Article
Language:English
Subjects:
Animals
APOPTOSIS
Apoptosis - physiology
Apoptosis Regulatory Proteins - metabolism
Cell death
Cells, Cultured
DROSOPHILA
Drosophila Proteins - metabolism
High-Temperature Requirement A Serine Peptidase 2
HtrA2/Omi
IN VITRO
IN VIVO
Inhibitor of Apoptosis Proteins - metabolism
IRRADIATION
MITOCHONDRIA
Mitochondria - physiology
Mitochondria - ultrastructure
Mitochondrial Proteins - metabolism
PROTEINS
RADIATION, THERMAL, AND OTHER ENVIRONMENTAL POLLUTANT EFFECTS ON LIVING ORGANISMS AND BIOLOGICAL MATERIALS
SERINE
Serine Endopeptidases - metabolism
Signal Transduction - physiology
STIMULI
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Summary:Despite the essential role of mitochondria in a variety of mammalian cell death processes, the involvement of mitochondrial pathway in Drosophila cell death has remained unclear. To address this, we cloned and characterized DmHtrA2, a Drosophila homolog of a mitochondrial serine protease HtrA2/Omi. We show that DmHtrA2 normally resides in mitochondria and is up-regulated by UV-irradiation. Upon receipt of apoptotic stimuli, DmHtrA2 is translocated to extramitochondrial compartment; however, unlike its mammalian counterpart, the extramitochondrial DmHtrA2 does not diffuse throughout the cytosol but stays near the mitochondria. RNAi-mediated knock-down of DmHtrA2 in larvae or adult flies results in a resistance to stress stimuli. DmHtrA2 specifically cleaves Drosophila inhibitor-of-apoptosis protein 1 (DIAP1), a cellular caspase inhibitor, and induces cell death both in vitro and in vivo as potent as other fly cell death proteins. Our observations suggest that DmHtrA2 promotes cell death through a cleavage of DIAP1 in the vicinity of mitochondria, which may represent a prototype of mitochondrial cell death pathway in evolution.
ISSN:0006-291X
1090-2104
DOI:10.1016/j.bbrc.2007.03.079