Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Experiment Videos

Mitochondrial protease Omi/HtrA2 enhances caspase activation through multiple pathways.

Y Suzuki1, K Takahashi-Niki, T Akagi

  • 1Laboratory for Motor System Neurodegeneration, RIKEN Brain Science Institute, 2-1 Hirosawa, Wako City, Saitama, Japan.

Cell Death and Differentiation
|November 8, 2003
PubMed
Summary

The mitochondrial protease Omi/HtrA2, when active, effectively promotes apoptosis by degrading inhibitor of apoptosis proteins (IAPs). Its protease activity is crucial for caspase activation and cell death pathways.

Related Concept Videos

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

Proper SUMO-1 conjugation is essential to DJ-1 to exert its full activities.

Cell death and differentiation·2005
Same author

The vasocontractive action of norepinephrine and serotonin in deep arterioles of rat cerebral gray matter.

The Tohoku journal of experimental medicine·2000
Same author

Age-related alterations in the activation of heat shock transcription factor 1 in rat hepatocytes.

Experimental cell research·2000
Same author

Identification of the novel developmentally regulated gene, Bdm2, which is highly expressed in fetal rat brain.

Brain research. Developmental brain research·2000
Same author

Inhibitory effect of insulin on bradykinin-induced venodilation.

Journal of hypertension·2000
Same author

[Werner's syndrome associated with acute myelofibrosis].

[Rinsho ketsueki] The Japanese journal of clinical hematology·2000

Area of Science:

  • Cellular Biology
  • Biochemistry
  • Molecular Biology

Background:

  • Omi/HtrA2 is a mitochondrial serine protease.
  • It is released into the cytosol during apoptosis.
  • Omi/HtrA2 neutralizes inhibitor of apoptosis proteins (IAPs) to promote caspase activation.

Purpose of the Study:

  • To investigate the role of Omi/HtrA2 protease activity in apoptosis and cell death.
  • To determine if Omi/HtrA2's protease function is essential for its ability to inhibit IAPs and activate caspases.

Main Methods:

  • Comparison of wild-type Omi/HtrA2 and a catalytically inactive mutant in response to apoptotic stimuli (UV, TNF).
  • Analysis of Omi/HtrA2 expression, XIAP binding, mitochondrial release, and XIAP protein levels.
  • In vitro cleavage of IAPs and inactivation of XIAP by recombinant Omi/HtrA2.

Related Experiment Videos

  • Assessment of Omi/HtrA2-induced mitochondrial outer membrane permeabilization and cytochrome c release.

    • Main Results:

    • Wild-type Omi/HtrA2 showed greater caspase activation than the inactive mutant.
    • UV irradiation led to reduced XIAP protein in cells expressing wild-type Omi/HtrA2.
    • Omi/HtrA2 directly cleaved IAPs and inactivated XIAP in vitro.
    • Extramitochondrial Omi/HtrA2 induced mitochondrial outer membrane permeabilization and cytochrome c release.

    Conclusions:

    • The protease activity of Omi/HtrA2 is essential for its IAP-inhibiting function.
    • Omi/HtrA2 promotes caspase activation through multiple pathways, including direct IAP cleavage and induction of mitochondrial outer membrane permeabilization.