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Redox Activation of Mitochondrial DAMPs and the Metabolic Consequences for Development of Autoimmunity.
Koenig, Andreas; Buskiewicz-Koenig, Iwona A.
Affiliation
  • Koenig A; Department of Microbiology and Immunology, SUNY Upstate Medical University, Syracuse, New York, USA.
  • Buskiewicz-Koenig IA; Department of Microbiology and Immunology, SUNY Upstate Medical University, Syracuse, New York, USA.
Antioxid Redox Signal ; 36(7-9): 441-461, 2022 03.
Article in En | MEDLINE | ID: mdl-35352943
ABSTRACT

Significance:

Reactive oxygen species (ROS) are well known to promote innate immune responses during and in the absence of microbial infections. However, excessive or prolonged exposure to ROS provokes innate immune signaling dysfunction and contributes to the pathogenesis of many autoimmune diseases. The relatively high basal expression of pattern recognition receptors (PRRs) in innate immune cells renders them prone to activation in response to minor intrinsic or extrinsic ROS misbalances in the absence of pathogens. Critical Issues A prominent source of ROS are mitochondria, which are also major inter-organelle hubs for innate immunity activation, since most PRRs and downstream receptor molecules are directly located either at mitochondria or at mitochondria-associated membranes. Due to their ancestral bacterial origin, mitochondria can also act as quasi-intrinsic self-microbes that mimic a pathogen invasion and become a source of danger-associated molecular patterns (DAMPs) that triggers innate immunity from within. Recent Advances The release of mitochondrial DAMPs correlates with mitochondrial metabolism changes and increased generation of ROS, which can lead to the oxidative modification of DAMPs. Recent studies suggest that ROS-modified mitochondrial DAMPs possess increased, persistent immunogenicity. Future Directions Herein, we discuss how mitochondrial DAMP release and oxidation activates PRRs, changes cellular metabolism, and causes innate immune response dysfunction by promoting systemic inflammation, thereby contributing to the onset or progression of autoimmune diseases. The future goal is to understand what the tipping point for DAMPs is to become oxidized, and whether this is a road without return. Antioxid. Redox Signal. 36, 441-461.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Autoimmune Diseases / Autoimmunity Limits: Humans Language: En Journal: Antioxid Redox Signal Journal subject: METABOLISMO Year: 2022 Document type: Article Affiliation country: United States

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Autoimmune Diseases / Autoimmunity Limits: Humans Language: En Journal: Antioxid Redox Signal Journal subject: METABOLISMO Year: 2022 Document type: Article Affiliation country: United States