Drosophila Omi, a mitochondrial-localized IAP antagonist and proapoptotic serine protease

Madhavi Challa, Srinivas Malladi, Brett J. Pellock, Douglas Dresnek, Shankar Varadarajan, Yuhui Yin, Kristin White, Shawn B. Bratton

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

Although essential in mammals, in flies the importance of mitochondrial outer membrane permeabilization for apoptosis remains highly controversial. Herein, we demonstrate that Drosophila Omi (dOmi), a fly homologue of the serine protease Omi/HtrA2, is a developmentally regulated mitochondrial intermembrane space protein that undergoes processive cleavage, in situ, to generate two distinct inhibitor of apoptosis (IAP) binding motifs. Depending upon the proapoptotic stimulus, mature dOmi is then differentially released into the cytosol, where it binds selectively to the baculovirus IAP repeat 2 (BIR2) domain in Drosophila IAP1 (DIAP1) and displaces the initiator caspase DRONC. This interaction alone, however, is insufficient to promote apoptosis, as dOmi fails to displace the effector caspase DrICE from the BIR1 domain in DIAP1. Rather, dOmi alleviates DIAP1 inhibition of all caspases by proteolytically degrading DIAP1 and induces apoptosis both in cultured cells and in the developing fly eye. In summary, we demonstrate for the first time in flies that mitochondrial permeabilization not only occurs during apoptosis but also results in the release of a bona fide proapoptotic protein.

Original languageEnglish (US)
Pages (from-to)3144-3156
Number of pages13
JournalEMBO Journal
Volume26
Issue number13
DOIs
StatePublished - Jul 11 2007
Externally publishedYes

Fingerprint

Serine Proteases
Drosophila
Apoptosis
Diptera
Initiator Caspases
Effector Caspases
Mammals
Caspases
Baculoviridae
Mitochondrial Membranes
Proteins
Cells
Cytosol
Membranes
Cultured Cells

Keywords

  • Apoptosis
  • DIAP1
  • dOmi
  • DRONC
  • Drosophila

ASJC Scopus subject areas

  • Genetics
  • Cell Biology

Cite this

Challa, M., Malladi, S., Pellock, B. J., Dresnek, D., Varadarajan, S., Yin, Y., ... Bratton, S. B. (2007). Drosophila Omi, a mitochondrial-localized IAP antagonist and proapoptotic serine protease. EMBO Journal, 26(13), 3144-3156. https://doi.org/10.1038/sj.emboj.7601745

Drosophila Omi, a mitochondrial-localized IAP antagonist and proapoptotic serine protease. / Challa, Madhavi; Malladi, Srinivas; Pellock, Brett J.; Dresnek, Douglas; Varadarajan, Shankar; Yin, Yuhui; White, Kristin; Bratton, Shawn B.

In: EMBO Journal, Vol. 26, No. 13, 11.07.2007, p. 3144-3156.

Research output: Contribution to journalArticle

Challa, M, Malladi, S, Pellock, BJ, Dresnek, D, Varadarajan, S, Yin, Y, White, K & Bratton, SB 2007, 'Drosophila Omi, a mitochondrial-localized IAP antagonist and proapoptotic serine protease', EMBO Journal, vol. 26, no. 13, pp. 3144-3156. https://doi.org/10.1038/sj.emboj.7601745
Challa M, Malladi S, Pellock BJ, Dresnek D, Varadarajan S, Yin Y et al. Drosophila Omi, a mitochondrial-localized IAP antagonist and proapoptotic serine protease. EMBO Journal. 2007 Jul 11;26(13):3144-3156. https://doi.org/10.1038/sj.emboj.7601745
Challa, Madhavi ; Malladi, Srinivas ; Pellock, Brett J. ; Dresnek, Douglas ; Varadarajan, Shankar ; Yin, Yuhui ; White, Kristin ; Bratton, Shawn B. / Drosophila Omi, a mitochondrial-localized IAP antagonist and proapoptotic serine protease. In: EMBO Journal. 2007 ; Vol. 26, No. 13. pp. 3144-3156.
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