Skip to Content
MilliporeSigma
  • Mitochondrial outer membrane integrity regulates a ubiquitin-dependent and NF-κB-mediated inflammatory response.

Mitochondrial outer membrane integrity regulates a ubiquitin-dependent and NF-κB-mediated inflammatory response.

The EMBO journal (2024-02-10)
Esmee Vringer, Rosalie Heilig, Joel S Riley, Annabel Black, Catherine Cloix, George Skalka, Alfredo E Montes-Gómez, Aurore Aguado, Sergio Lilla, Henning Walczak, Mads Gyrd-Hansen, Daniel J Murphy, Danny T Huang, Sara Zanivan, Stephen Wg Tait
ABSTRACT

Mitochondrial outer membrane permeabilisation (MOMP) is often essential for apoptosis, by enabling cytochrome c release that leads to caspase activation and rapid cell death. Recently, MOMP has been shown to be inherently pro-inflammatory with emerging cellular roles, including its ability to elicit anti-tumour immunity. Nonetheless, how MOMP triggers inflammation and how the cell regulates this remains poorly defined. We find that upon MOMP, many proteins localised either to inner or outer mitochondrial membranes are ubiquitylated in a promiscuous manner. This extensive ubiquitylation serves to recruit the essential adaptor molecule NEMO, leading to the activation of pro-inflammatory NF-κB signalling. We show that disruption of mitochondrial outer membrane integrity through different means leads to the engagement of a similar pro-inflammatory signalling platform. Therefore, mitochondrial integrity directly controls inflammation, such that permeabilised mitochondria initiate NF-κB signalling.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Cyclosporin A, 97.0-101.5% (on dried basis)
Sigma-Aldrich
Monoclonal Anti-Actin antibody produced in mouse, clone AC-40, ascites fluid
Sigma-Aldrich
Anti-Ubiquitin Antibody, Lys63-Specific, clone Apu3, rabbit monoclonal, clone Apu3, from rabbit
Sigma-Aldrich
Anti-March5 Antibody, serum, from rabbit
Sigma-Aldrich
Oligomycin from Streptomyces diastatochromogenes, ≥90% total oligomycins basis (HPLC)
Sigma-Aldrich
Antimycin A from Streptomyces sp.
Sigma-Aldrich
Rotenone, ≥95%