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PMID:17397804

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Citation

Igaki, T, Suzuki, Y, Tokushige, N, Aonuma, H, Takahashi, R and Miura, M (2007) Evolution of mitochondrial cell death pathway: Proapoptotic role of HtrA2/Omi in Drosophila. Biochem. Biophys. Res. Commun. 356:993-7

Abstract

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.

Links

PubMed Online version:10.1016/j.bbrc.2007.03.079

Keywords

Animals; Apoptosis/physiology; Apoptosis Regulatory Proteins/metabolism; Cells, Cultured; Drosophila; Drosophila Proteins/metabolism; Inhibitor of Apoptosis Proteins/metabolism; Mitochondria/physiology; Mitochondria/ultrastructure; Mitochondrial Proteins/metabolism; Serine Endopeptidases/metabolism; Signal Transduction/physiology

Significance

Annotations

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

DROME:DIAP1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q9VFJ3

F

Seeded From UniProt

complete

DROME:DIAP1

involved_in

GO:0043066: negative regulation of apoptotic process

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:HTRA2

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q24306

F

Seeded From UniProt

complete

DROME:HTRA2

located_in

GO:0005758: mitochondrial intermembrane space

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

DROME:HTRA2

enables

GO:0004252: serine-type endopeptidase activity

ECO:0000315: mutant phenotype evidence used in manual assertion

F

Seeded From UniProt

complete

DROME:HTRA2

involved_in

GO:0042981: regulation of apoptotic process

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:IAP1

involved_in

GO:0043066: negative regulation of apoptotic process

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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