JIM 2024;
1 (4): e636
DOI: 10.61012_202411_636
The link between mitochondria and inflammation: a brief review
Topic: Inherited Metabolic Diseases in Paediatric Age
Category: Review
Abstract
Inflammation plays a central role in various diseases, including autoimmune disorders and viral infections, and can worsen conditions caused by non-inflammatory stressors. Mitochondria, with their bacterial-like properties, are involved in regulating inflammation. Damaged mitochondria release components such as mtDNA into the cytosol, triggering innate immune responses. The DNA sensor cGAS activates the STING pathway, leading to a type I-IFN response and inflammasome activation. MtDNA is also a key activator of the NLRP3 inflammasome via a reactive oxygen species (ROS)-dependent mechanism. Mitochondrial ROS and mtDNA act as damage-associated molecular patterns (DAMPs), which are critical for inflammasome activation and regulate regulated cell death (RCD). Mitochondrial components such as cytochrome c, cardiolipin, and N-formyl peptides can trigger inflammatory responses through various receptors like TLR9 and RAGE. Excessive mtDAMP signaling is tightly regulated to prevent unwarranted inflammation, with mechanisms like apoptosis and autophagy modulating immune responses. Dysregulated mtDAMP signaling contributes to diseases such as Systemic Lupus Erythematosus, Crohn's disease, and Parkinson’s disease, and can affect viral infections and cancer progression. Mitochondrial dysfunctions play a significant role in abnormal innate immune responses. Although mitochondrial-targeting therapies for inflammation are largely unexplored, they present a potential avenue for treatment, especially given the limited pharmacological options available. In conclusion, while mitochondria are key regulators of inflammation, further research is needed to fully understand their role and develop effective therapeutic strategies to address mitochondrial dysfunction and its connection to various inflammatory diseases.
To cite this article
The link between mitochondria and inflammation: a brief review
JIM 2024;
1 (4): e636
DOI: 10.61012_202411_636
Publication History
Submission date: 30 Sep 2024
Revised on: 28 Oct 2024
Accepted on: 04 Nov 2024
Published online: 29 Nov 2024