Mitochondrial reactive zones in antiviral innate immunity

• Published in: Biochimica et biophysica acta. General subjects Vol. 1865; no. 3; p. 129839
• Main Authors: Yasukawa, Kai, Koshiba, Takumi
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.03.2021
• Subjects: Adaptor Proteins, Signal Transducing - genetics; Adaptor Proteins, Signal Transducing - immunology; Animals; apoptosis; DEAD Box Protein 58 - genetics; DEAD Box Protein 58 - immunology; energy metabolism; Gene Expression Regulation; genes; Host-Pathogen Interactions - genetics; Host-Pathogen Interactions - immunology; Humans; immune response; Immunity, Innate; Inflammasomes; Innate immunity; MAVS; MicroRNAs - genetics; MicroRNAs - immunology; Mitochondria; Mitochondria - genetics; Mitochondria - immunology; Mitochondria - virology; Mitochondrial Membranes - immunology; Mitochondrial Membranes - virology; NLR Family, Pyrin Domain-Containing 3 Protein - genetics; NLR Family, Pyrin Domain-Containing 3 Protein - immunology; NLRP3 inflammasomes; Receptors, Immunologic - genetics; Receptors, Immunologic - immunology; RLR pathway; RNA virus; RNA Virus Infections - genetics; RNA Virus Infections - immunology; RNA Virus Infections - pathology; RNA Virus Infections - virology; RNA Viruses - genetics; RNA Viruses - immunology; RNA Viruses - pathogenicity; Signal Transduction; therapeutics; RLR pathway; Innate immunity; MAVS; Mitochondria; NLRP3 inflammasomes; RNA virus
• ISSN: 0304-4165; 1872-8006; 1872-8006
• DOI: 10.1016/j.bbagen.2020.129839

Mitochondria are multi-functioning organelles that participate in a wide range of biologic processes from energy metabolism to cellular suicide. Mitochondria are also involved in the cellular innate immune response against microorganisms or environmental irritants, particularly in mammals. Mitochondrial-mediated innate immunity is achieved by the activation of two discrete signaling pathways, the NLR family pyrin domain-containing 3 inflammasomes and the retinoic acid-inducible gene I-like receptor pathway. In both pathways, a mitochondrial outer membrane adaptor protein, called mitochondrial antiviral signaling MAVS, and mitochondria-derived components play a key role in signal transduction. In this review, we discuss current insights regarding the fundamental phenomena of mitochondrial-related innate immune responses, and review the specific roles of various mitochondrial subcompartments in fine-tuning innate immune signaling events. We propose that specific targeting of mitochondrial functions is a potential therapeutic approach for the management of infectious diseases and autoinflammatory disorders with an excessive immune response. •Mitochondria act as a central hub for innate immune signaling.•Damaged mitochondria release mitochondrial-related alarmins.•Activation of NLRP3 inflammasomes requires a mitochondrial surface platform.•MAVS is a mitochondrial adaptor involved in the RLR signaling pathway.•Dynamic properties of mitochondria fine-tune innate immune signaling.