Related Experiment Video
Updated: May 31, 2025
07:54
Highly Efficient Transfection of Human THP-1 Macrophages by Nucleofection
Published on: September 2, 2014
46.8K
Mitochondria complex III-generated superoxide is essential for IL-10 secretion in macrophages
Joshua S Stoolman1, Rogan A Grant1, Leah K Billingham2
1Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
Science Advances
|January 22, 2025
Summary
Mitochondrial electron transport chain complex III deficiency in macrophages increases susceptibility to infection and shock. Superoxide generation by complex III is crucial for releasing anti-inflammatory IL-10 after TLR stimulation.
Area of Science:
- Immunology
- Mitochondrial Biology
- Cellular Respiration
Background:
- Mitochondrial electron transport chain (ETC) function impacts macrophage immune responses.
- The precise mechanisms linking ETC function to macrophage immunity are not fully elucidated.
Purpose of the Study:
- To investigate the role of ETC complex III (CIII) in macrophage immune responses.
- To understand how CIII deficiency affects susceptibility to viral infection and endotoxic shock.
Main Methods:
- Generated mice with CIII-deficient macrophages.
- Utilized bone marrow-derived macrophages (BMDMs) for in vitro studies.
- Stimulated BMDMs with Toll-like receptor (TLR) agonists (TLR3, TLR4) and cytokines (IL-4).
- Assessed IL-10 release and susceptibility to influenza A virus (IAV) and lipopolysaccharide (LPS).
Main Results:
- Mice with CIII-deficient macrophages showed increased susceptibility to IAV and LPS-induced endotoxic shock.
- CIII-deficient BMDMs produced less IL-10 following TLR3 or TLR4 stimulation.
- Restoring respiration with alternative oxidase (AOX) did not reverse shock susceptibility or restore IL-10 release.
- Protein kinase A (PKA) activation rescued IL-10 release in CIII-deficient BMDMs.
- IL-4 responses remained unaffected by CIII deficiency.
Conclusions:
- Mitochondrial CIII-generated superoxide is essential for IL-10 release in response to TLR stimulation.
- CIII function in macrophages plays a critical role in regulating innate immune responses and host defense.
Related Concept Videos
01:43Electron Transport Chain: Complex III and IV
7.0K
During the electron transport chain, electrons from NADH and FADH2 are first transferred to complexes I and II, respectively. These two complexes then transfer the electrons to ubiquinol, which carries them further to complex III. Complex III passes the electrons across the intermembrane space to Cyt c, which carries them further to complex IV. Complex IV donates electrons to oxygen and reduces it to water. As electrons pass through complexes I, III, and IV, the energy released aids the pumping...
7.0K
01:41The Supercomplexes in the Crista Membrane
2.5K
The mitochondrial cristae membrane is the primary site for the oxidative phosphorylation (OXPHOS) process of energy conversion mediated through respiratory complexes I to V. These complexes have been widely studied for decades, and it has been proven that they form supramolecular structures called respiratory supercomplexes (SC). These higher-order complexes may be crucial in maintaining the biochemical structure and improving the physiological activity of the individual complexes while...
2.5K
01:46Electron Transport Chain: Complex I and II
10.7K
The mitochondrial electron transport chain (ETC) is the main energy generation system in the eukaryotic cells. However, mitochondria also produce cytotoxic reactive oxygen species (ROS) due to the large electron flow during oxidative phosphorylation. While Complex I is one of the primary sources of superoxide radicals, ROS production by Complex II is uncommon and may only be observed in cancer cells with mutated complexes.
ROS generation is regulated and maintained at moderate levels necessary...
ROS generation is regulated and maintained at moderate levels necessary...
10.7K
01:37Mitochondria
10.1K
Mitochondria are eukaryotic cellular organelles that are known to produce energy through a process called oxidative phosphorylation. Besides their primary function, mitochondria are involved in various cellular processes, including cell growth, differentiation, signaling, metabolism, and senescence. Age-related changes cause a decline in mitochondrial quality and integrity due to increased mitochondrial mutations and oxidative damage. Thus, aging can severely impact mitochondrial functions,...
10.1K
01:30The Electron Transport Chain
16.0K
The electron transport chain or oxidative phosphorylation is an exothermic process in which free energy released during electron transfer reactions is coupled to ATP synthesis. This process is a significant source of energy in aerobic cells, and therefore inhibitors of the electron transport chain can be detrimental to the cell's metabolic processes.
Inhibitors of the electron transport chain
Rotenone, a widely used pesticide, prevents electron transfer from Fe-S cluster to ubiquinone or Q...
Inhibitors of the electron transport chain
Rotenone, a widely used pesticide, prevents electron transfer from Fe-S cluster to ubiquinone or Q...
16.0K
01:45Mitochondrial Membranes
7.7K
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,...
7.7K