Mitochondria in innate immune signaling

• Published in: Translational research : the journal of laboratory and clinical medicine Vol. 202; pp. 52 - 68
• Main Authors: Banoth, Balaji, Cassel, Suzanne L.
• Format: Journal Article
• Language: English
• Published: United States 01.12.2018
• Subjects: Alarmins - metabolism; Animals; DNA, Mitochondrial - genetics; Humans; Immunity, Innate; Mitochondria - metabolism; Models, Biological; Signal Transduction; IRF, interferon regulatory factor; RIG-I, retinoic acid inducible gene I; RLR, retinoic acid inducible gene like receptor; MARCH5, membrane-associated ring finger (C3HC4) 5; JNK, cJUN NH2-terminal kinase; ATP, adenosine tri-phosphate; TANK, TRAF family member-associated NFκB activator; HMGB1, high mobility group box protein 1; MPT, mitochondrial permeability transition; TLR, Toll Like Receptor; n-fp, n-formyl peptides; TRIF, TIR-domain-containing adapter-inducing interferon β; mtDNA, mitochondrial DNA; NFκB, Nuclear factor κ B; LRR, leucine rich repeat; fMet, N-formylated methionine; MFN1/2, mitofusin; HIF, hypoxia-inducible factor; PPAR, peroxisome proliferator-accelerated receptor; MAVS, mitochondrial antiviral signaling; PRRs, pathogen recognition receptors; STING, stimulator of interferon gene; IL, interleukin; Cgas, cyclic GMP-AMP synthase; CAPS, cryopyrin associated periodic syndromes; LPS, lipopolysaccharide; TFAM, mitochondrial transcription factor A; CLR, C-type lectin receptor; MAPK, mitogen-activated protein kinase; TBK1, TANK Binding Kinase 1; CARD, caspase activation and recruitment domain; CREB, cAMP response element binding protein; MAVS, mitochondrial antiviral signaling protein; mROS, mitochondrial ROS; TAK1, transforming growth factor-β-activated kinase 1; ASK1, apoptosis signal-regulating kinase 1; PAMP, pathogen associated molecular pattern; NADH, nicotinamide adenine dinucleotide; MOMP, mitochondrial outer membrane permeabilization; ESCIT, evolutionarily conserved signaling intermediate in the toll pathway; ROS, reactive oxygen species; ETC, electron transport chain; NRF2, nuclear factor erythroid 2-related factor 2; TUFM, Tu translation elongation factor; IFN, interferon; DAMP, damage associated molecular pattern; FPR, formyl peptide receptor; CL, cardiolipin; NOD, nucleotide-binding oligomerization domain; TCA, Tri-carboxylic acid; TRAF6, tumor necrosis factor receptor-associated factor 6; ASC, Apoptosis Associated Speck like protein containing CARD; MyD88, myeloid differentiation primary response 88; NBD, nucleotide binding domain; NLR, NOD like receptor
• ISSN: 1931-5244; 1878-1810; 1878-1810
• DOI: 10.1016/j.trsl.2018.07.014

Mitochondria are functionally versatile organelles. In addition to their conventional role of meeting the cell's energy requirements, mitochondria also actively regulate innate immune responses against infectious and sterile insults. Components of mitochondria, when released or exposed in response to dysfunction or damage, can be directly recognized by receptors of the innate immune system and trigger an immune response. In addition, despite initiation that may be independent from mitochondria, numerous innate immune responses are still subject to mitochondrial regulation as discrete steps of their signaling cascades occur on mitochondria or require mitochondrial components. Finally, mitochondrial metabolites and the metabolic state of the mitochondria within an innate immune cell modulate the precise immune response and shape the direction and character of that cell's response to stimuli. Together, these pathways result in a nuanced and very specific regulation of innate immune responses by mitochondria.