Mitochondria as Molecular Platforms Integrating Multiple Innate Immune Signalings. Issue 1 (6th January 2017)

• Record Type: Journal Article
• Authors: Monlun, Marie; Hyernard, Caroline; Blanco, Patrick; Lartigue, Lydia; Faustin, Benjamin
• Is Part Of: Journal of molecular biology. Volume 429:Issue 1(2017)
• Page Start: 1
• Page End: 13
• Publication Date: 2017-01-06
• Subjects: DC dendritic cell -- PRR pattern recognition receptor -- PAMP pathogen-associated molecular pattern -- DAMP danger-associated molecular pattern -- MAPK mitogen-activated protein kinase -- IFN interferon -- TLR Toll-like receptor -- NLR nucleotide-oligomerization domain-like receptor -- RIG-I retinoic acid-inducible gene-I -- RLR RIG-I-like receptor -- OXPHOS oxidative phosphorylation -- MAVS mitochondrial antiviral signaling -- OMM outer mitochondrial membrane -- mtROS mitochondrial reactive oxygen species -- RC respiratory chain -- ROS reactive oxygen species -- LPS lipopolysaccharide -- TCA tricarboxylic -- SDH succinate dehydrogenase -- LRR leucine-rich repeat -- ER endoplasmic reticulum -- oxmtDNA oxidized mtDNA -- MPT mitochondrial permeability transition -- HK hexokinase -- mtDNA mitochondrial DNA -- HIF-1α hypoxia-inducing factor 1 alpha -- MSU monosodium urate -- ASC apoptosis-associated speck-like protein containing a CARD -- IFNAR interferon-α/β receptor -- FAS Fas Cell Surface Death Receptor -- VDAC voltage-dependent anion channel -- AMPK AMP-activated protein kinase; immunology -- inflammation -- metabolism -- mitochondria -- inflammasome; Molecular biology -- Periodicals; Biology -- Periodicals; Biochemistry -- Periodicals; Bacteriology -- Periodicals; Molecular Biology -- Periodicals; Biochemistry -- Periodicals; Biologie moléculaire -- Périodiques; Biologie -- Périodiques; Biochimie -- Périodiques; Moleculaire biologie; Biochemistry; Biology; Molecular biology; Periodicals; 572.805
• DOI: 10.1016/j.jmb.2016.10.028
• Languages: English
• ISSNs: 0022-2836

Abstract

Abstract: The immune system of vertebrates confers protective mechanisms to the host through the sensing of stress-induced agents expressed during infection or cell stress. Among them, the first line of host defense composed of the innate immune sensing of these agents by pattern recognition receptors enables downstream adaptive immunity to be primed, mediating the body's appropriate response to clear infection and tissue damage. Mitochondria are «bacteria within» that allowed the emergence of functional eukaryotic cells by positioning themselves as the cell powerhouse and an initiator of cell death programs. It is striking to consider that such ancestral bacteria, which had to evade host defense at some point to develop evolutionary endosymbiosis, have become instrumental for the modern eukaryotic cell in alerting the immune system against various insults including infection by other pathogens. Mitochondria have indeed become critical regulators of innate immune responses to both pathogens and cell stress. They host numerous modulators, which play a direct role into the assembly of innate sensing machineries that trigger host immune response in both sterile and non-sterile conditions. Several lines of evidence indicate the existence of a complex molecular interplay between mechanisms involved in inflammation and metabolism. Mitochondrial function seems to participate in innate immunity at various stages as diverse as the transcriptional regulation of inflammatory cytokines and chemokines and their maturation by inflammasomes. Here, we review the mechanisms by which mitochondria orchestrate innate immune responses at different levels by promoting a cellular metabolic reprogramming and the cytosolic immune signaling cascades. Graphical Abstract: Highlights: Mitochondria are «bacteria within» that are crucially involved in multiple host innate immune responses to infection (bacteria and viruses) and sterile cell stress. Mitochondrial function seems to control innate immunity at various stages as diverse as the transcriptional regulation of inflammatory cytokines and chemokines and their maturation by inflammasomes. Mitochondria orchestrate innate immune responses at different levels by promoting a cellular metabolic reprogramming and the cytosolic immune signaling cascades. Mitochondria host a myriad of molecular components involved in innate immune machineries. Mitochondria integrate innate immune sensing of pathogens and cell stress and propagate signals through the release of its components to alert cytosolic sentinels.