Aromatic hydrocarbon receptors in mitochondrial biogenesis and function

Sahebnasagh, Adeleh; Hashemi, Javad; Khoshi, Amirhosein; Saghafi, Fatemeh; Avan, Razieh; Faramarzi, Fatemeh; Azimi, Saeed; Habtemariam, Solomon; Sureda, Antoni; Khayatkashani, Maryam; Safdari, Mohammadreza; Ghaleno, Hassan Rezai; Soltani, Hosseinali; Kashani, Hamid Reza Khayat

doi:10.1016/j.mito.2021.09.012

Cited by 7 publications

(3 citation statements)

References 258 publications

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“…The aryl hydrocarbon receptor (AhR), a cytosolic ligand-activated transcription factor, regulates the expression of numerous genes, including those involved in the response to environmental pollutants, polarization of microglia, myelination, and inflammation [47][48][49]. In the CNS, AhR exerts anti-inflammatory properties on microglia and astrocytes, promoting restorative neurogenesis and post-insult tissue regeneration [50].…”

Section: Lactate and Mental Illnessmentioning

confidence: 99%

The Role of Lactylation in Mental Illness: Emphasis on Microglia

et al. 2023

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A paradigm shift is currently taking place in the etiopathogenesis of neuropsychiatric disorders as immunometabolism is replacing the earlier neurotransmitter model. According to the new concept, cellular bioenergetics drives information processing in the central nervous system; therefore, neuropathology is conceptualized as a direct consequence of impaired metabolism. Along the same lines, endoplasmic reticulum stress and gut barrier dysfunction are emerging as novel targets in schizophrenia and affective disorders, linking immune responses to cellular distress. Furthermore, microglia, the brain’s innate immune cells, acquire energy through oxidative phosphorylation, while in the resting state, and glycolysis upon activation, contributing to lactate accumulation and reduced brain pH. The same metabolic signature characterizes neuropsychiatric disorders as the central nervous system derives adenosine triphosphate from aerobic glycolysis, upregulating lactate and generating an acidic environment. Although known for over three decades, the link between dysmetabolism and neuropathology was poorly defined until the discovery of brain-resident innate lymphoid cells, including natural killer cells, and lactylation of histone and nonhistone proteins. In this perspective article, we examine three anti-inflammatory microglial systems relevant for neuropsychiatry: lactate, oxytocin, and the aryl hydrocarbon receptor. We also discuss potential interventions for restoring microglial homeostasis.

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Section: Lactate and Mental Illnessmentioning

confidence: 99%

The Role of Lactylation in Mental Illness: Emphasis on Microglia

et al. 2023

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“…Additionally, a ligand–AhR complex can function as a coactivator of E2 promoter-binding factor 1 (E2F1): a transcription factor that is crucial for the cell cycle transition from the G1 phase to the S phase [ 92 , 106 ]. The binding of AhR to the hypophosphorylated “active” form of the retinoblastoma tumor suppressor protein (pRb) leads to cell growth arrest in the G1/S phase of the cell cycle [ 107 ]. It is reported that two mechanisms contribute to this effect.…”

Section: Ahr Expression Functions and Signalingmentioning

confidence: 99%

Aryl Hydrocarbon Receptor in Oxidative Stress as a Double Agent and Its Biological and Therapeutic Significance

Grishanova

Perepechaeva

2022

IJMS

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The aryl hydrocarbon receptor (AhR) has long been implicated in the induction of a battery of genes involved in the metabolism of xenobiotics and endogenous compounds. AhR is a ligand-activated transcription factor necessary for the launch of transcriptional responses important in health and disease. In past decades, evidence has accumulated that AhR is associated with the cellular response to oxidative stress, and this property of AhR must be taken into account during investigations into a mechanism of action of xenobiotics that is able to activate AhR or that is susceptible to metabolic activation by enzymes encoded by the genes that are under the control of AhR. In this review, we examine various mechanisms by which AhR takes part in the oxidative-stress response, including antioxidant and prooxidant enzymes and cytochrome P450. We also show that AhR, as a participant in the redox balance and as a modulator of redox signals, is being increasingly studied as a target for a new class of therapeutic compounds and as an explanation for the pathogenesis of some disorders.

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“…In conclusion, the effects of endogenous ligands or low doses-exogenous ligands (as opposed to persistent exogenous ligands [ 72 , 86 ]) would have cell-protective effects as they only lead to transient AhR activation and possibly mitogenesis promoting effects ( Figure 3 ) [ 87 ].…”

Section: Ahr As a Crucial Player In Environmental Pollutant-induced Mitochondrial Dysfunctionmentioning

confidence: 99%

Mitochondrial Dysfunction as a Hallmark of Environmental Injury

Duarte-Hospital

Tête

Brial

et al. 2021

Cells

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Environmental factors including diet, sedentary lifestyle and exposure to pollutants largely influence human health throughout life. Cellular and molecular events triggered by an exposure to environmental pollutants are extremely variable and depend on the age, the chronicity and the doses of exposure. Only a fraction of all relevant mechanisms involved in the onset and progression of pathologies in response to toxicants has probably been identified. Mitochondria are central hubs of metabolic and cell signaling responsible for a large variety of biochemical processes, including oxidative stress, metabolite production, energy transduction, hormone synthesis, and apoptosis. Growing evidence highlights mitochondrial dysfunction as a major hallmark of environmental insults. Here, we present mitochondria as crucial organelles for healthy metabolic homeostasis and whose dysfunction induces critical adverse effects. Then, we review the multiple mechanisms of action of pollutants causing mitochondrial toxicity in link with chronic diseases. We propose the Aryl hydrocarbon Receptor (AhR) as a model of “exposome receptor”, whose activation by environmental pollutants leads to various toxic events through mitochondrial dysfunction. Finally, we provide some remarks related to mitotoxicity and risk assessment.

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Aromatic hydrocarbon receptors in mitochondrial biogenesis and function

Cited by 7 publications

References 258 publications

The Role of Lactylation in Mental Illness: Emphasis on Microglia

The Role of Lactylation in Mental Illness: Emphasis on Microglia

Aryl Hydrocarbon Receptor in Oxidative Stress as a Double Agent and Its Biological and Therapeutic Significance

Mitochondrial Dysfunction as a Hallmark of Environmental Injury

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