Reactive oxygen species from mitochondrial complex III are induced by NCLX to promote astrocytic STAT3‐linked transcription and dementia‐related pathology
Our data suggest that dementia-associated factors induce site-specific mROS production and that CIII-ROS promote precise post-translational redox modifications and amplify STAT3-linked signaling and changes in gene expression. Together, our findings reveal CIII-ROS as an important node of mitochondrial-nuclear communication in pathogenic conditions, whereby mROS transients are converted into long-lasting changes in gene transcription and cell function. CIII-ROS and redox signaling offer new therapeutic opportunities for aging-associated neurological disorders.
Authors
- Samantha M. Meadows (ORCID: https://orcid.org/0000-0002-0954-5379)
- Daniel Barnett (ORCID: https://orcid.org/0000-0002-1340-4413)
- Caroline Booraem (ORCID: https://orcid.org/0009-0000-3294-6253)
- Haopeng Xiao (ORCID: https://orcid.org/0000-0002-4166-647X)
- Edward T. Chouchani (ORCID: https://orcid.org/0000-0002-9203-8094)
- Adam L. Orr (ORCID: https://orcid.org/0000-0003-0338-7709)
- Till S. Zimmer (ORCID: https://orcid.org/0000-0002-6869-3697)
- Fernando Palaguachi (ORCID: https://orcid.org/0000-0001-5403-7093)
- Anna G. Orr (ORCID: https://orcid.org/0000-0002-4036-4277)
Institutions
- Harvard University (US)
- Cornell University (US)
- MIND Research Institute (US)
- Tri-Institutional PhD Program in Chemical Biology (US)
- Dana-Farber Cancer Institute (US)
- Weill Cornell Medicine (US)
Publication Details
- Journal
- Alzheimer s & Dementia
- Published
- 2024-12-01
- DOI
- https://doi.org/10.1002/alz.084464
- Primary Topic
- Tryptophan and brain disorders
- Type
- article
- Field-Weighted Citation Impact
- 0.00