Related Experiment Video

Updated: Sep 2, 2025

Inner Mitochondrial Membrane Sensitivity to Na+ Reveals Partially Segmented Functional CoQ Pools
05:27

Inner Mitochondrial Membrane Sensitivity to Na+ Reveals Partially Segmented Functional CoQ Pools

Published on: July 20, 2022

2.0K

Bilirubin stabilizes the mitochondrial membranes during NLRP3 inflammasome activation

Yufei Li1, Hongda Sheng1, Ziwei Yan1

  • 1Pharmaceutical Informatics Institute, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.

Biochemical Pharmacology
|August 9, 2022
PubMed

Insights

Bilirubin stabilizes mitochondrial membranes, reducing inflammation by inhibiting NLRP3 inflammasome activation. This suggests bilirubin as a potential therapeutic for inflammasome-related diseases.

Area of Science:

  • Mitochondrial biology
  • Immunology
  • Pharmacology

Background:

  • Mitochondria are key sensors of cellular stress, releasing mitochondrial reactive oxygen species (mt-ROS) that activate the NLRP3 inflammasome.
  • Regulating mitochondrial morphology and function offers a strategy against inflammation.
  • Bilirubin, at physiological concentrations, has shown anti-inflammatory effects by inhibiting NF-κB and inflammasome pathways.

Purpose of the Study:

  • To investigate the specific anti-NLRP3 inflammasome effects of bilirubin.
  • To elucidate the mechanism by which bilirubin modulates NLRP3 inflammasome activation, focusing on mitochondrial function and mt-ROS release.

Main Methods:

  • Assessed IL-1β and TNF-α release, ASC oligomer/speck formation, and pro-caspase-1 recruitment.
  • Evaluated bilirubin's effect on mt-ROS release due to its antioxidant properties.
  • Analyzed mitochondrial morphology and membrane potential in live macrophages using high-content imaging.

Main Results:

  • Bilirubin was found to target and stabilize mitochondrial membranes during NLRP3 inflammasome activation.
  • Bilirubin effectively inhibited key markers of NLRP3 inflammasome activation, including cytokine release and inflammasome complex assembly.
  • Bilirubin mitigated the release of mt-ROS and preserved mitochondrial membrane potential.

Conclusions:

  • Bilirubin demonstrates a direct inhibitory effect on NLRP3 inflammasome activation.
  • Bilirubin acts by stabilizing mitochondrial membranes and reducing mt-ROS production.
  • Defined doses of bilirubin show potential as a mitochondria-targeted therapeutic for inflammasome-related diseases.
Keywords:
BilirubinHigh-content imaging analysisMitochondrial morphofunctionNLRP3 inflammasome

More Related Videos

Activation and Measurement of NLRP3 Inflammasome Activity Using IL-1β in Human Monocyte-derived Dendritic Cells09:04

Activation and Measurement of NLRP3 Inflammasome Activity Using IL-1β in Human Monocyte-derived Dendritic Cells

Published on: May 22, 2014

21.0K
Study of Endoplasmic Reticulum and Mitochondria Interactions by In Situ Proximity Ligation Assay in Fixed Cells09:34

Study of Endoplasmic Reticulum and Mitochondria Interactions by In Situ Proximity Ligation Assay in Fixed Cells

Published on: December 10, 2016

24.8K

Related Concept Videos

Translocation of Proteins into the Mitochondria01:19

Translocation of Proteins into the Mitochondria

Mitochondrial precursors are translocated to the internal subcompartments via independent mechanisms involving distinct protein machineries called translocases.
Sorting of outer membrane proteins:
Mitochondrial outer membrane proteins are of two types: the transmembrane, beta-barrel porins, and the membrane-anchored, alpha-helical proteins. Beta-barrel porin precursors are translocated by the TOM complex and inserted into the outer mitochondrial membrane by the SAM complex. In contrast,...
3.2K
Mitochondrial Protein Sorting01:39

Mitochondrial Protein Sorting

Mitochondria are double-membrane organelles of the eukaryotes involved in cellular metabolism, signaling, ATP synthesis, and programmed cell death.  Each of these processes requires specific proteins and enzymes that must be correctly sorted to the right mitochondrial subcompartment for the proper functioning of the organelle.
Most of these mitochondrial proteins are encoded by the nucleus and imported to the mitochondria as unfolded or loosely folded precursors. Mitochondrial precursors...
4.4K
Mitochondrial Membranes01:45

Mitochondrial Membranes

A single mitochondrion is a bean-shaped organelle enclosed by a double-membrane system. The outer membrane of mitochondria is smooth and contains many porins - the integral membrane transporters. Porins enable free diffusion of ions and small uncharged molecules through the outer mitochondrial membrane but limit the transport of molecules larger than 5000 Daltons. Further, the outer mitochondrial membrane forms a unique structure called membrane contact sites with other subcellular organelles,...
12.0K
Porin Insertion in the Outer Mitochondrial Membrane01:12

Porin Insertion in the Outer Mitochondrial Membrane

Porins are beta-barrel proteins translocated to the mitochondrial outer membrane through the TOM complex into the intermembrane space. Porin precursors bind TIM chaperones within the intermembrane space and are guided to the Sorting and Assembly Machinery complex or SAM complex on the outer mitochondrial membrane.
Three models describe the assembly of porins by the SAM complex and their insertion into the outer membrane. Model 1 suggests that porins are assembled outside the SAM channel as the...
3.2K