Mitochondria, Oxidative Stress and Innate Immunity

Chen, Yuxin; Zhou, Zhenhua; Wang, Min

doi:10.3389/fphys.2018.01487

Cited by 271 publications

(216 citation statements)

References 105 publications

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“…Thus, oxidized DNA represents a prototypic damage-associated molecular pattern (DAMP) with important implications for infection, sterile inflammation and autoimmunity [225]. Mitochondria-derived ROS can induce activation of innate immune responses, including activation of inflammasome, cGAS-STING and NF-κB signalling pathways (for review: [226]). The ambient levels of ROS are important for homeostasis of cells, whereas excessive ROS are important in killing pathogens.…”

Section: Reactive Oxygen Species and Nitrogen Speciesmentioning

confidence: 99%

Replication Stress, DNA Damage, Inflammatory Cytokines and Innate Immune Response

Ragu

Matos-Rodrigues

Lopez

2020

Genes

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Complete and accurate DNA replication is essential to genome stability maintenance during cellular division. However, cells are routinely challenged by endogenous as well as exogenous agents that threaten DNA stability. DNA breaks and the activation of the DNA damage response (DDR) arising from endogenous replication stress have been observed at pre-or early stages of oncogenesis and senescence. Proper detection and signalling of DNA damage are essential for the autonomous cellular response in which the DDR regulates cell cycle progression and controls the repair machinery. In addition to this autonomous cellular response, replicative stress changes the cellular microenvironment, activating the innate immune response that enables the organism to protect itself against the proliferation of damaged cells. Thereby, the recent descriptions of the mechanisms of the pro-inflammatory response activation after replication stress, DNA damage and DDR defects constitute important conceptual novelties. Here, we review the links of replication, DNA damage and DDR defects to innate immunity activation by pro-inflammatory paracrine effects, highlighting the implications for human syndromes and immunotherapies.Genes 2020, 11, 409 2 of 26 formed when nascent transcripts re-anneal to their template DNA, displacing the non-template strand as single-stranded DNA (ssDNA) [12]. Elevated R-loop levels cause DNA damage and genome instability. The loss of RNA processing and regulatory factors increases R-loop levels, causing R-loop dependent DNA damage in eukaryotic cells [13][14][15][16].DNA breaks and activation of the DNA damage response (DDR), arising from endogenous replication stress, have been observed at early or precancerous stages, and adaptation to replication stress plays an important role in tumour development [17][18][19][20]. The DDR protects genome stability through the precise coordination of a network of pathways, ensuring faithful transmission of genetic material, including DNA replication, repair and recombination, cell cycle checkpoint and chromosome segregation. Ultimately, these autonomous cell responses induce senescence or cell death [21][22][23][24][25]. All these processes prevent the proliferation of cells bearing DNA damage and/or genetic rearrangements. In agreement, syndromes caused by mutations in DDR and/or DNA repair factors are often associated with high genetic instability, cancer predisposition and premature ageing [24,[26][27][28]. In addition to these cell-autonomous responses, protective process(es) also act at the organism level. Such mechanism(s) involve the modification of the cellular microenvironment and ultimately the activation of innate immunity.The inflammatory response is a universal cell-intrinsic response to infections or tissue damage. Inflammation, which is triggered when innate immune cells detect infection, for example, eliminates the initial cause of cell injury, clears out necrotic cells and tissues damaged from the original insult and from the inflammatory process, and initiates ...

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Section: Reactive Oxygen Species and Nitrogen Speciesmentioning

confidence: 99%

Replication Stress, DNA Damage, Inflammatory Cytokines and Innate Immune Response

Ragu

Matos-Rodrigues

Lopez

2020

Genes

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“…; Chen et al. ; Citrin & Mitchell, ). Although oxidative stress appears to be an accident, this is unlikely to be true.…”

Section: Reactive Oxygen Species Needed and Dangerousmentioning

confidence: 99%

“…The nature of oxidative stress includes unspecific oxidation of intracellular molecules, with potentially detrimental effects on cell function and survival (Misra, Sarwat, Bhakuni, Tuteja, & Tuteja, 2009). Oxidative stress often occurs in the course of unpredictable events that mainly target individual cells, such as inflammation, irradiation or poisoning, for example with cigarette smoke (Boukhenouna et al 2018;Chen et al 2018;Citrin & Mitchell, 2017). Although oxidative stress appears to be an accident, this is unlikely to be true.…”

Section: Reactive Oxygen Species Needed and Dangerousmentioning

confidence: 99%

NADPH oxidase‐derived reactive oxygen species: Dosis facit venenum

Schröder

2019

Experimental Physiology

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New Findings What is the topic of this review? Within this review, the role of reactive oxygen species in cellular homeostasis, physiology and pathophysiology is discussed. What advances does it highlight? The review provides new concepts of how reactive oxygen species influence gene expression, energy consumption and other aspects of the life of a cell. Furthermore, a model is provided to illustrate how reactive oxygen species elicit specific oxidation of target molecules. Abstract Reactive oxygen species (ROS) have a long history of bad reputation. They are needed and effective in host defense, but on the contrary may induce situations of oxidative stress. Besides that, within recent years several soft functions (functions that may occur and are not directly connected to an effect, but may influence signaling in an indirect manner) of NADPH oxidases have been discovered, which are slowly eroding the image of the solely dangerous ROS. NADPH oxidase‐derived ROS serve to ease or enable signal transduction and to maintain homeostasis. However, there is still an enormous lag in the knowledge concerning target proteins and how ROS can elicit specific signalling in different cells and tissues. The present review summarizes some important functions of Nox2 and Nox4. Furthermore, although highly speculative, a model is provided of how those NADPH oxidases might be able to oxidize target proteins in a specific way. Many concepts mentioned in this review represent my personal view and are supported only in part by published studies.

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“…In addition to the cellular mechanisms of protection against stresses, there is also protection at the level of the whole organism. This higher order, coordinated protection is primarily mediated by the inflammatory and immune systems (Chen et al, 2018,Ferrucci and Fabbri, 2018,Franceschi et al, 2018,O'Neil et al, 2018.…”

Section: Introductionmentioning

confidence: 99%

ADAM17-triggered TNF signalling protects the ageing Drosophila retina from lipid droplet mediated degeneration

Muliyil

Levet

Düsterhöft

et al. 2020

Preprint

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Animals have evolved multiple mechanisms to protect themselves from the cumulative effects of age-related cellular damage. Here we reveal an unexpected link between the TNF (tumour necrosis factor) inflammatory pathway, triggered by the metalloprotease ADAM17/TACE, and a lipid droplet (LD)-mediated mechanism of protecting retinal cells from age related degeneration. Loss of ADAM17, TNF and the TNF receptor Grindelwald in pigmented glial cells of the Drosophila retina leads to age related degeneration of both glia and neurons, preceded by an abnormal accumulation of glial LDs. We show that the glial LDs initially buffer the cells against damage caused by neuronally generated reactive oxygen species (ROS), but that in later life the LDs dissipate, leading to the release of toxic peroxidated lipids. Finally, we demonstrate the existence of a conserved pathway in human iPS-derived microglia-like cells, which are central players in neurodegeneration. Overall, we have discovered a pathway mediated by TNF signalling acting not as a trigger of inflammation, but as a cytoprotective factor in the retina.

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Mitochondria, Oxidative Stress and Innate Immunity

Cited by 271 publications

References 105 publications

Replication Stress, DNA Damage, Inflammatory Cytokines and Innate Immune Response

Replication Stress, DNA Damage, Inflammatory Cytokines and Innate Immune Response

NADPH oxidase‐derived reactive oxygen species: Dosis facit venenum

ADAM17-triggered TNF signalling protects the ageing Drosophila retina from lipid droplet mediated degeneration

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