Summary of project PR002581
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 PR002581. The data can be accessed directly via it's Project DOI: 10.21228/M81C34 This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
| Project ID: | PR002581 |
| Project DOI: | doi: 10.21228/M81C34 |
| Project Title: | Mitochondrial complex III-derived reactive oxygen species amplify immunometabolic changes in astrocytes and promote dementia pathology |
| Project Summary: | Neurodegenerative disorders alter mitochondrial functions, including the production of reactive oxygen species (ROS). Mitochondrial complex III (CIII) generates ROS implicated in redox signaling, but its triggers, temporal dynamics, targets, and disease relevance are not clear. Using site-selective suppressors and genetic manipulations together with live mitochondrial ROS imaging and multiomic profiling, we found that CIII is a dominant source of ROS production in astrocytes exposed to neuropathology-related stimuli. Astrocytic CIII-ROS production was dependent on nuclear factor-κB (NF-κB) and the mitochondrial sodium-calcium exchanger (NCLX) and caused oxidation of select cysteines within immune- and metabolism-associated proteins linked to neurological disease. CIII-ROS amplified metabolomic and pathology-associated transcriptional changes in astrocytes, with STAT3 activity as a major mediator, and facilitated neuronal toxicity. Therapeutic suppression of CIII-ROS in mice decreased dementia-linked tauopathy and neuroimmune cascades and extended lifespan. Our findings establish CIII-ROS as an important immunometabolic signal transducer and tractable therapeutic target in neurodegenerative disease. |
| Institute: | Weill Cornell Medicine |
| Department: | Appel Alzheimer's Disease Research Institute, Feil Family Brain and Mind Research Institute |
| Laboratory: | Orr Laboratory |
| Last Name: | Barnett |
| First Name: | Daniel |
| Address: | 413 East 69th St, New York, NY, 10021, USA |
| Email: | dmb4001@med.cornell.edu |
| Phone: | 5854659449 |
| Funding Source: | National Institute on Aging, National Institutes of Health |
Summary of all studies in project PR002581
| Study ID | Study Title | Species | Institute | Analysis(* : Contains Untargted data) | Release Date | Version | Samples | Download(* : Contains raw data) |
|---|---|---|---|---|---|---|---|---|
| ST004106 | Mitochondrial complex III-derived reactive oxygen species amplify immunometabolic changes in astrocytes and promote dementia pathology | Mus musculus | Weill Cornell Medicine | MS | 2025-09-07 | 1 | 16 | Uploaded data (648.6M)* |
