Summary of project PR002218
This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR002218. The data can be accessed directly via it's Project DOI: 10.21228/M8XF95 This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
| Project ID: | PR002218 |
| Project DOI: | doi: 10.21228/M8XF95 |
| Project Title: | Mitochondria complex III is essential for IL-10 secretion in macrophages independent of respiration |
| Project Summary: | Mitochondrial electron transport chain (ETC) function is linked to macrophage function. However, mechanisms underlying mitochondrial ETC control of macrophage immune responses are not fully understood. We used genetic tools to examine the necessity of mitochondrial electron transport chain (ETC)-dependent respiration and the production of reactive oxygen species (mtROS) in macrophage immune responses. Here we report that mitochondrial ETC complex III (CIII)-deficient mouse macrophages, which have impaired macrophage respiration and mtROS production, exhibit increased susceptibility to influenza A virus and LPS-induced endotoxic shock. Mitochondrial CIII-deficient bone marrow-derived macrophages (BMDMs) produced IL-10 but exhibit dampened release following TLR3 or TLR4 stimulation in vitro. Surprisingly, restoring mitochondrial respiration without generating mtROS in mitochondrial CIII-deficient macrophages with Ciona intestinalis alternative oxidase (AOX) is not sufficient to reverse the increased vulnerability to LPS-induced endotoxic shock or rescue IL-10 release in vitro. However, activation of PKA, an mtROS-responsive pathway2, was sufficient to rescue BMDM IL-10 release following LPS stimulation. Additionally, mitochondrial CIII impairment in macrophages does not affect canonical responses to interleukin-4 (IL-4) stimulation. Thus, our results highlight necessity of mitochondrial ROS but not respiration in release of IL-10. |
| Institute: | Northwestern University, Feinberg School of Medicine |
| Department: | Pulmonary |
| Laboratory: | Chandel |
| Last Name: | Stoolman |
| First Name: | Joshua |
| Address: | 303 E Superior Street |
| Email: | joshua.stoolman@northwestern.edu |
| Phone: | 7343559440 |
Summary of all studies in project PR002218
| Study ID | Study Title | Species | Institute | Analysis(* : Contains Untargted data) | Release Date | Version | Samples | Download(* : Contains raw data) |
|---|---|---|---|---|---|---|---|---|
| ST003588 | Mitochondria complex III is essential for IL-10 secretion in macrophages independent of respiration | Mus musculus | Northwestern University, Feinberg School of Medicine | MS | 2024-12-20 | 1 | 55 | Uploaded data (4G)* |
