The aryl hydrocarbon receptor interacts with ATP5α1, a subunit of the ATP synthase complex, and modulates mitochondrial function

Tappenden, Dorothy M.; Lynn, Scott G.; Crawford, R. J.; Lee, KangAe; Vengellur, Ajith; Kaminski, Norbert E.; Thomas, Russell S.; LaPres, John J.

doi:10.1016/j.taap.2011.05.004

Cited by 43 publications

(51 citation statements)

References 48 publications

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“…6A). As AhR has been previously described to induce mitochondrial hyperpolarization (Tappenden et al, 2011) and appeared to be involved in NO production ( Supplementary Fig. 4A), we next decided to further test the involvement of this receptor under our experimental conditions.…”

Section: Inhibition Of B[a]p-induced No Production Prevented the Relamentioning

confidence: 99%

Benzo[a]pyrene-induced nitric oxide production acts as a survival signal targeting mitochondrial membrane potential

Hardonnière

Huc

Podechard

et al. 2015

Toxicology in Vitro

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Benzo[a]pyrene (B[a]P), the prototype molecule of polycyclic aromatic hydrocarbons, exhibits genotoxic and carcinogenic effects, which has led the International Agency for Research on Cancer to recognize it as a human carcinogen. Besides the well-known apoptotic signals triggered by B[a]P, survival signals have also been suggested to occur, both signals likely involved in cancer promotion. Our previous work showed that B[a]P induced an hyperpolarization of mitochondrial membrane potential (ΔΨm) in rat hepatic epithelial F258 cells. Elevated ΔΨm plays a role in tumor development and progression, and nitric oxide (NO) has been suggested to be responsible for increases in ΔΨm. The present study therefore aimed at evaluating the impact of B[a]P on NO level in F258 cells, and at testing the putative role for NO as a survival signal, notably in link with ΔΨm. Our data demonstrated that B[a]P exposure resulted in an NO production which was dependent upon the activation of the inducible NO synthase. This enzyme activation involved AhR and possibly p53 activation. Preventing NO production not only increased B[a]P-induced cell death but also blocked mitochondrial hyperpolarization. This therefore points to a role for NO as a survival signal upon B[a]P exposure, possibly targeting ΔΨm.

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Section: Inhibition Of B[a]p-induced No Production Prevented the Relamentioning

confidence: 99%

Benzo[a]pyrene-induced nitric oxide production acts as a survival signal targeting mitochondrial membrane potential

Hardonnière

Huc

Podechard

et al. 2015

Toxicology in Vitro

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“…We focused on energy metabolic processes since they may be under significant selection pressure due to (i) increased ATP demand for PAH detoxification and to maintain cellular homeostasis; (ii) effects of PAHs on mitochondrial integrity 17 as well as cardiac development and function 18–20 potentially altering oxygen and nutrient circulation; and (iii) presumed role of the aryl hydrocarbon receptor, a key protein involved in PAH metabolism, as a mitochondrial regulator. 21 …”

Section: Introductionmentioning

confidence: 99%

Cost of Tolerance: Physiological Consequences of Evolved Resistance to Inhabit a Polluted Environment in Teleost Fish Fundulus heteroclitus

Jayasundara

Fernando

Osterberg

et al. 2017

Environ. Sci. Technol.

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Anthropogenic stressors, including pollutants, are key evolutionary drivers. It is hypothesized that rapid evolution to anthropogenic changes may alter fundamental physiological processes (e.g., energy metabolism), compromising an organism’s capacity to respond to additional stressors. The Elizabeth River (ER) Superfund site represents a “natural-experiment” to explore this hypothesis in several subpopulations of Atlantic killifish that have evolved a gradation of resistance to a ubiquitous pollutant—polycyclic aromatic hydrocarbons (PAH). We examined bioenergetic shifts and associated consequences in PAH-resistant killifish by integrating genomic, physiological, and modeling approaches. Population genomics data revealed that genomic regions encoding bioenergetic processes are under selection in PAH-adapted fish from the most contaminated ER site and ex vivo studies confirmed altered mitochondrial function in these fish. Further analyses extending to differentially PAH-resistant subpopulations showed organismal level bioenergetic shifts in ER fish that are associated with increased cost of living, decreased performance, and altered metabolic response to temperature stress—an indication of reduced thermal plasticity. A movement model predicted a higher energetic cost for PAH-resistant subpopulations when seeking an optimum habitat. Collectively, we demonstrate that pollution adaption and inhabiting contaminated environments may result in physiological shifts leading to compromised organismal capacity to respond to additional stressors.

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“…In addition, the AHR has been linked to mitochondria-to-nucleus stress signaling (Biswas et al ., 2008). Moreover, the AHR can induce changes in metabolic flux, independent of transcription (Tappenden et al ., 2011). Given that mitochondria are critical components of cellular metabolism, the main sites for energy production, and that many pathophysiological effects linked to TCDD exposure (e.g.…”

Section: Introductionmentioning

confidence: 99%

“…Interestingly, these interactions were lost upon exposure to TCDD (Tappenden et al ., 2013; Tappenden et al ., 2011). In addition, the cytosolic binding partners of the AHR (i.e., AIP and HSP90) can bind the mitochondrial translocase of outer-membrane complex, and facilitate mitochondrial import of proteins lacking classic mitochondrial targeting sequences (MTS), such as the AHR.…”

Section: Introductionmentioning

confidence: 99%

Mitochondrial-targeted aryl hydrocarbon receptor and the impact of 2,3,7,8-tetrachlorodibenzo-p-dioxin on cellular respiration and the mitochondrial proteome

Hwang

Dornbos

Steidemann

et al. 2016

Toxicology and Applied Pharmacology

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The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor within the Per-Arnt-Sim (PAS) domain superfamily. Exposure to the most potent AHR ligand, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), is associated with various pathological effects including metabolic syndrome. While research over the last several years has demonstrated a role for oxidative stress and metabolic dysfunction in AHR-dependent TCDD-induced toxicity, the role of the mitochondria in this process has not been fully explored. Our previous research suggested that a portion of the cellular pool of AHR could be found in the mitochondria (mitoAHR). Using a protease protection assay with digitonin extraction, we have now shown that this mitoAHR is localized to the inter-membrane space (IMS) of the organelle. TCDD exposure induced a degradation of mitoAHR similar to that of cytosolic AHR. Furthermore, siRNA-mediated knockdown revealed that translocase of outer-mitochondrial membrane 20 (TOMM20) was involved in the import of AHR into the mitochondria. In addition, TCDD altered cellular respiration in an AHR-dependent manner to maintain respiratory efficiency as measured by oxygen consumption rate (OCR). Stable isotope labeling by amino acids in cell culture (SILAC) identified a battery of proteins within the mitochondrial proteome influenced by TCDD in an AHR-dependent manner. Among these, 17 proteins with |fold changes| ≥ 2 are associated with various metabolic pathways, suggesting a role of mitochondrial retrograde signaling in TCDD-mediated pathologies. Collectively, these studies suggest that mitoAHR is localized to the IMS and AHR-dependent TCDD-induced toxicity, including metabolic dysfunction, wasting syndrome, and hepatic steatosis, involves mitochondrial dysfunction.

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The aryl hydrocarbon receptor interacts with ATP5α1, a subunit of the ATP synthase complex, and modulates mitochondrial function

Cited by 43 publications

References 48 publications

Benzo[a]pyrene-induced nitric oxide production acts as a survival signal targeting mitochondrial membrane potential

Benzo[a]pyrene-induced nitric oxide production acts as a survival signal targeting mitochondrial membrane potential

Cost of Tolerance: Physiological Consequences of Evolved Resistance to Inhabit a Polluted Environment in Teleost Fish Fundulus heteroclitus

Mitochondrial-targeted aryl hydrocarbon receptor and the impact of 2,3,7,8-tetrachlorodibenzo-p-dioxin on cellular respiration and the mitochondrial proteome

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