Mitochondrial DNA, oxidants, and innate immunity.

Abstract

Mitochondrial oxidant damage, including damage to mitochondrial DNA (mtDNA) is a feature of both severe microbial infections and inflammation arising from sterile (non-infectious) sources such as tissue trauma. Damaged mitochondria release intact or oxidized fragments of mtDNA into the cytoplasm, which represent oxidant injury, and the fragments promote a spontaneous innate immune response, exemplifying a modern frontier of immunological research. MtDNA and mitochondrial-derived oxidants are central factors in activating at least three innate immune pathways involving the TLR9 (Toll-like receptor 9), the NLRP3 (NACHT, LRR and PYD domains-containing protein-3) inflammasome, and the cGAS (cyclic AMP-GMP synthase) pathway. The events that allow mtDNA to escape from damaged mitochondria and from damaged cells are incompletely known, but the presence of cytoplasmic mtDNA and cell-free mtDNA as immune regulators are important for understanding the cell's capacity for protecting mitochondrial quality control (MQC) and cell viability during inflammatory states.

• Authors: Claude A Piantadosi
• Journal: Free radical biology & medicine (Free Radic Biol Med) Vol. 152 Pg. 455-461 (05 20 2020) ISSN: 1873-4596 [Electronic] United States
• PMID: 31958498 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S., Review)
• Copyright: Copyright © 2020 Elsevier Inc. All rights reserved.

Chemical References

• DNA, Mitochondrial
• Inflammasomes
• Oxidants

Topics

• DNA, Mitochondrial (genetics)
• Immunity, Innate
• Inflammasomes
• Mitochondria (genetics)
• Oxidants