Abstract
Mitochondria play critical roles in a wide variety of cellular functions beyond their intrinsic role as the energy powerhouse of the cell. Accumulating evidence has shown that mitochondria are deeply involved in innate immune responses to a variety of pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs). Mitochondria serve as a signalling platform for antiviral innate immunity and are involved in the regulation of the NLRP3 inflammasome, an intracellular signalling complex required for the secretion of the proinflammatory cytokines interleukin (IL)-1β and IL-18. These findings suggest that mitochondrial conditions and integrity profoundly influence the extent and duration of inflammation. However, exposure of cells to various cytotoxic stressors easily causes damage to mitochondria and destroys mitochondrial integrity. If the damage is not severe, mitochondrial functions are maintained depending on the mitochondrial quality control system; however, once the damage exceeds capacity, cell-death–inducing signals are elicited by the mitochondria. Thus, mitochondrial sensing and stress response, as well as mitochondrial quality control, may be critically involved not only in the overall cellular response but also in the regulation of inflammation.
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Abbreviations
- ASC:
-
Apoptosis-associated speck-like protein containing a C-terminal CARD
- BMDM:
-
Bone-marrow–derived macrophage
- CARD:
-
Caspase recruitment domain
- Cardif:
-
CARD adaptor inducing IFN-β
- CCCP:
-
Carbonyl cyanide m-chlorophenylhydrazone
- DAMPs:
-
Damage-associated molecular patterns
- DC:
-
Dendritic cell
- Δψ m :
-
Membrane potential across the inner mitochondrial membrane
- DRP1:
-
Dynamin-related protein 1
- ECSIT:
-
Evolutionarily conserved signalling intermediate in Toll pathways
- gC1qR:
-
Receptor for globular head domain of complement component C1q
- IL:
-
Interleukin
- IPS-1:
-
Interferon-β promoter stimulator 1
- IRF:
-
Interferon regulatory factor
- IRGM:
-
Immunity-related GTPase family M protein
- MAVS:
-
Mitochondria-associated viral sensor
- MDA5:
-
Melanoma-differentiation-associated gene 5
- MFN:
-
Mitofusin
- mtDNA:
-
mitochondrial DNA
- NLR:
-
Nucleotide oligomerisation domain (NOD)-like receptor
- NLRP3:
-
NOD-like receptor family, pyrin domain containing 3
- NLRX1:
-
NOD-like receptor family member X1
- NFP:
-
N-formyl peptide
- OPA1:
-
Optic atrophy protein 1
- PAMPs:
-
Pathogen-associated molecular patterns
- PINK1:
-
PTEN-induced putative kinase 1
- RIG-I:
-
Retinoic acid inducible gene-I
- ROS:
-
Reactive oxygen species
- TLR:
-
Toll-like receptor
- VISA:
-
Virus-induced signalling adaptor
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Takeda, K., Sadatomi, D., Tanimura, S. (2016). Roles of Mitochondrial Sensing and Stress Response in the Regulation of Inflammation. In: Miyasaka, M., Takatsu, K. (eds) Chronic Inflammation. Springer, Tokyo. https://doi.org/10.1007/978-4-431-56068-5_23
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DOI: https://doi.org/10.1007/978-4-431-56068-5_23
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