The role of mitophagy in innate immune responses triggered by mitochondrial stress
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(2020) 18:186
REVIEW
Open Access
The role of mitophagy in innate immune responses triggered by mitochondrial stress Yinjuan Song1, Yang Zhou2,3 and Xiangmei Zhou1*
Abstract Mitochondria are important cellular organelles involved in many different functions, from energy generation and fatty acid oxidation to cell death regulation and immune responses. Accumulating evidence indicates that mitochondrial stress acts as a key trigger of innate immune responses. Critically, the dysfunctional mitochondria can be selectively eliminated by mitophagy. The elimination of dysfunctional mitochondria may function as an effective way employed by mitophagy to keep the immune system in check. In addition, mitophagy can be utilized by pathogens for immune evasion. In this review, we summarize how mitochondrial stress triggers innate immune responses and the roles of mitophagy in innate immunity and in infection, as well as the molecular mechanisms of mitophagy. Keywords: Mitophagy, Mitochondrial stress, Innate immunity, Infection, Mitophagy mechanisms
Introduction The innate immune system is the first line of defense against pathogen infection. Pathogens are initially sensed by pattern-recognition receptors (PRRs) of the innate immune system, which bind to pathogen-associated molecular patterns (PAMPs), including the structural components, nucleic acids and proteins of pathogenic microorganisms [1]. The PRRs include four families: Toll-like receptors (TLRs), nucleotide oligomerization domain (NOD)-like receptors (NLRs), C-type lectin receptors (CLRs) and retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs) [2, 3]. Ligand binding initiates activation of PRRs, resulting in the activation of nuclear factor-κappa B (NF-κB), mitogen-activated protein kinases (MAPKs), inflammasomes and interferon regulatory factors (IRFs), and subsequent production of pro-inflammatory cytokines, chemokines, type I interferon (IFN) and co-stimulatory molecules [1]. Multiple * Correspondence: [email protected] 1 Key Laboratory of Animal Epidemiology and Zoonosis, Ministry of Agriculture, National Animal Transmissible Spongiform Encephalopathy Laboratory, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China Full list of author information is available at the end of the article
studies have established crosstalk between innate immune signals and mitochondria. Mitochondria are dynamic, double-membrane-bound eukaryotic organelles that originated from an ancient α-proteobacterium more than 1.5–2.5 billion years ago [4–6]. Mitochondria maintain their own genetic material, mitochondrial DNA (mtDNA), which is a small, double-stranded circular molecule that only encodes 13 necessary protein subunits of the oxidative phosphorylation system (OXPHOS), and about 99% of mitochondrial proteins are nuclear DNA encoded [7]. Mitochondria perform multiple functions in cells, which are the energy factory of the cell. In addition to energy generation, their crucial roles in metabolism include amino acid and fatty acid metabolism and
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