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Mitochondrial reactive zones in antiviral innate immunity

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ELSEVIER
DOI: 10.1016/j.bbagen.2020.129839

Keywords

Innate immunity; MAVS; Mitochondria; NLRP3 inflammasomes; RLR pathway; RNA virus

Funding

  1. Ministry of Education, Culture, Sports, Science, and Technology of Japan (JSPS KAKENHI) [17H03667, 18H04863, 20H04914]
  2. Naito Foundation
  3. Grants-in-Aid for Scientific Research [20H04914, 18H04863, 17H03667] Funding Source: KAKEN

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Mitochondria are multi-functioning organelles involved in a wide range of biological processes and innate immune responses against microorganisms or irritants. Activation of two signaling pathways, NLR family pyrin domain-containing 3 inflammasomes and retinoic acid-inducible gene I-like receptor pathway, is crucial for mitochondrial-mediated innate immunity. Targeting mitochondrial functions could be a potential therapeutic approach for managing infectious diseases and autoinflammatory disorders.
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.

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