Mitochondria as Molecular Platforms Integrating Multiple Innate Immune Signalings

Monlun, Marie; Hyernard, Caroline; Blanco, Patrick; Lartigue, Lydia; Faustin, Benjamin

doi:10.1016/j.jmb.2016.10.028

Cited by 74 publications

(60 citation statements)

References 76 publications

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“…Mitochondria are known to play a role in innate and adaptive immune responses, inflammation, and signaling in response to infection [14, 104]. However, it is unknown how mitochondrial dysfunction affects the immune system or the inflammatory response in autism.…”

Section: Alternative Mechanisms Of Asd Pathogenesismentioning

confidence: 99%

Evidence of Mitochondrial Dysfunction in Autism: Biochemical Links, Genetic‐Based Associations, and Non‐Energy‐Related Mechanisms

Griffiths

Levy

2017

Oxidative Medicine and Cellular Longevity

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Autism spectrum disorder (ASD), the fastest growing developmental disability in the United States, represents a group of neurodevelopmental disorders characterized by impaired social interaction and communication as well as restricted and repetitive behavior. The underlying cause of autism is unknown and therapy is currently limited to targeting behavioral abnormalities. Emerging studies suggest a link between mitochondrial dysfunction and ASD. Here, we review the evidence demonstrating this potential connection. We focus specifically on biochemical links, genetic-based associations, non-energy related mechanisms, and novel therapeutic strategies.

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Section: Alternative Mechanisms Of Asd Pathogenesismentioning

confidence: 99%

Evidence of Mitochondrial Dysfunction in Autism: Biochemical Links, Genetic‐Based Associations, and Non‐Energy‐Related Mechanisms

Griffiths

Levy

2017

Oxidative Medicine and Cellular Longevity

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“…Mitochondria are now recognized as key regulators of cytokine production, employing several pathways of up‐regulating cytokine transcripts and cell surface receptors. Dimerization and nuclear translocation of PKM2 could not be implicated in up‐regulating PD‐L1, giving rise to the concept that the excess production of cytokines and the enhancement of PD‐L1 expression may be separable.…”

Section: Metabolic Control Of Pd‐l1 Expressionmentioning

confidence: 99%

The immunoinhibitory PD-1/PD-L1 pathway in inflammatory blood vessel disease

Weyand

Berry

Goronzy

2017

Journal of Leukocyte Biology

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Because of their vital function, the wall structures of medium and large arteries are immunoprivileged and protected from inflammatory attack. That vascular immunoprivilege is broken in atherosclerosis and in vasculitis, when wall-invading T cells and macrophages (Mϕ) promote tissue injury and maladaptive repair. Historically, tissue-residing T cells were studied for their antigen specificity, but recent progress has refocused attention to antigen-nonspecific regulation, which determines tissue access, persistence, and functional differentiation of T cells. The coinhibitory receptor PD-1, expressed on T cells, delivers negative signals when engaged by its ligand PD-L1, expressed on dendritic cells, Mϕ, and endothelial cells to attenuate T cell activation, effector functions, and survival. Through mitigating signals, the PD-1 immune checkpoint maintains tissue tolerance. In line with this concept, dendritic cells and Mϕs from patients with the vasculitic syndrome giant cell arteritis (GCA) are PD-L1 ; including vessel-wall-embedded DCs that guard the vascular immunoprivilege. GCA infiltrates in the arterial walls are filled with PD-1 T cells that secrete IFN-γ, IL-17, and IL-21; drive inflammation-associated angiogenesis; and facilitate intimal hyperplasia. Conversely, chronic tissue inflammation in the atherosclerotic plaque is associated with an overreactive PD-1 checkpoint. Plaque-residing Mϕs are PD-L1 , a defect induced by their addiction to glucose and glycolytic breakdown. PD-L1 Mϕs render patients with coronary artery disease immunocompromised and suppress antiviral immunity, including protective anti-varicella zoster virus T cells. Thus, immunoinhibitory signals affect several domains of vascular inflammation; failing PD-L1 in vasculitis enables unopposed immunostimulation and opens the flood gates for polyfunctional inflammatory T cells, and excess PD-L1 in the atherosclerotic plaque disables tissue-protective T cell immunity.

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“…Accumulating studies have indicated that in addition to being efficient cell powerhouses due to their roles in ATP production through oxidative phosphorylation and the synthesis of critical cellular components, such as nucleotides and amino acids, mitochondria can regulate the activation of the NLRP3 and NLRP6 inflammasomes, microbial-and host-derived metabolites, the glycolysis process and metabolism to affect immune responses [13]. Importantly, the activation of PRR programing sends signals to mitochondria, which, in turn, undergo a metabolic switch from oxidative phosphorylation to glycolysis to prepare the cells for defense against pathogens [14]. This effect also places mitochondria in a frontier position in microbial-triggered PRR activation and subsequent signal transduction.…”

Section: Mitochondria Regulate Metabolism and Immunitymentioning

confidence: 99%

Operation of mitochondrial machinery in viral infection-induced immune responses

Lai

Luo

2018

Biochemical Pharmacology

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Mitochondria have been recognized as ancient bacteria that contain evolutionary endosymbionts. Metabolic pathways and inflammatory signals interact within mitochondria in response to different stresses, such as viral infections. In this commentary, we address several interesting questions, including (1) how do mitochondrial machineries participate in immune responses; (2) how do mitochondria mediate antiviral immunity; (3) what mechanisms involved in mitochondrial machinery, including the downregulation of mitochondrial DNA (mtDNA), disturbances of mitochondrial dynamics, and the induction of mitophagy and regulation of apoptosis, have been adopted by viruses to evade antiviral immunity; (4) what mechanisms involve the regulation of mitochondrial machineries in antiviral therapeutics; and (5) what are the potential challenges and perspectives in developing mitochondria-targeting antiviral treatments? This commentary provides a comprehensive review of the roles and mechanisms of mitochondrial machineries in immunity, viral infections and related antiviral therapeutics.

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Mitochondria as Molecular Platforms Integrating Multiple Innate Immune Signalings

Cited by 74 publications

References 76 publications

Evidence of Mitochondrial Dysfunction in Autism: Biochemical Links, Genetic‐Based Associations, and Non‐Energy‐Related Mechanisms

Evidence of Mitochondrial Dysfunction in Autism: Biochemical Links, Genetic‐Based Associations, and Non‐Energy‐Related Mechanisms

The immunoinhibitory PD-1/PD-L1 pathway in inflammatory blood vessel disease

Operation of mitochondrial machinery in viral infection-induced immune responses

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