The aryl hydrocarbon receptor interacts with ATP5{alpha}1, a subunit of the ATP synthase complex, and modulates mitochondrial function

Journal Article · Mon Aug 01 00:00:00 EDT 2011 · Toxicology and Applied Pharmacology

DOI:https://doi.org/10.1016/j.taap.2011.05.004· OSTI ID:21587809

Tappenden, Dorothy M; Lynn, Scott G ^[1]; Crawford, Robert B ^[2]; Lee, KangAe; Vengellur, Ajith ^[1]; Kaminski, Norbert E ^[3]; Thomas, Russell S ^[4]

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1. Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, MI 48824-1319 (United States)
2. Department of Pharmacology and Toxicology, Michigan State University, East Lansing, MI 48824-1319 (United States)
3. Center for Integrative Toxicology, Michigan State University, East Lansing, MI 48824-1319 (United States)
4. The Hamner Institutes for Health Sciences, Research Triangle Park, NC 27709 (United States)

Dioxins, including 2,3,7,8 tetrachlorodibenzo-p-dioxin (TCDD), produce a wide range of toxic effects in mammals. Most, if not all, of these toxic effects are regulated by the aryl hydrocarbon receptor (AHR). The AHR is a ligand activated transcription factor that has been shown to interact with numerous proteins capable of influencing the receptor's function. The ability of secondary proteins to alter AHR-mediated transcriptional events, a necessary step for toxicity, led us to determine whether additional interacting proteins could be identified. To this end, we have employed tandem affinity purification (TAP) of the AHR in Hepa1c1c7 cells. TAP of the AHR, followed by mass spectrometry (MS) identified ATP5{alpha}1, a subunit of the ATP synthase complex, as a strong AHR interactor in the absence of ligand. The interaction was lost upon exposure to TCDD. The association was confirmed by co-immunoprecipitation in multiple cell lines. In addition, cell fractionation experiments showed that a fraction of the AHR is found in the mitochondria. To ascribe a potential functional role to the AHR:ATP5{alpha}1 interaction, TCDD was shown to induce a hyperpolarization of the mitochondrial membrane in an AHR-dependent and transcription-independent manner. These results suggest that a fraction of the total cellular AHR pool is localized to the mitochondria and contributes to the organelle's homeostasis. - Highlights: > The AHR interacts with the mitochondrial protein, ATP5{alpha}1. > Cell fractionation experiments show that the AHR can be found in the mitochondria. > TCDD-exposure induces a hyperpolarization of the mitochondrial inner membrane. > The hyperpolarization is AHR-dependent. > The hyperpolarization occurs without altering ATP levels within the cell.

• OSTI ID: 21587809
• Journal Information: Toxicology and Applied Pharmacology, Vol. 254, Issue 3; Other Information: DOI: 10.1016/j.taap.2011.05.004; PII: S0041-008X(11)00173-6; Copyright (c) 2011 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); ISSN 0041-008X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
AFFINITY
ATP
DIOXIN
FRACTIONATION
HOMEOSTASIS
HYDROCARBONS
INTERACTIONS
LIGANDS
MAMMALS
MASS SPECTROSCOPY
MEMBRANES
MITOCHONDRIA
RECEPTORS
TOXICITY
TRANSCRIPTION FACTORS
ANIMALS
CELL CONSTITUENTS
HETEROCYCLIC COMPOUNDS
MEMBRANE PROTEINS
NUCLEOTIDES
ORGANIC COMPOUNDS
ORGANIC OXYGEN COMPOUNDS
PROTEINS
SEPARATION PROCESSES
SPECTROSCOPY
VERTEBRATES