Evidence map›Paper›PMID 24497629›Full record

ArticleThe Journal of biological chemistry2014

Mitochondrial targeting of cytochrome P450 (CYP) 1B1 and its role in polycyclic aromatic hydrocarbon-induced mitochondrial dysfunction.

Seema Bansal, Adrian N Leu, Frank J Gonzalez, F Peter Guengerich, Anindya Roy Chowdhury, Hindupur K Anandatheerthavarada, Narayan G Avadhani

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.

0numbers the graph read from it
0cells of the map it votes in
35citing papers in PubMed
10.2field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

35 citing papers in PubMed, 83 citations in OpenAlex.

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  12. NullInternational journal of molecular sciences · 2021
    Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 3 institutions in 1 country.

Seema BansalFrom the Department of Animal Biology and the Mari Lowe Center for Comparative Oncology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104.
Adrian N Leu
Frank J Gonzalez
F Peter Guengerich
Anindya Roy Chowdhury
Hindupur K Anandatheerthavarada
Narayan G Avadhani
University of Pennsylvania · USNational Institutes of Health · USVanderbilt University · US

Funding

Xenobiotic ReceptorsZIABC005708 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI GONZALEZ, FRANK J · 2009 to 2025
$16.4M
Role of Mitochondria-Targeted CYP2D6 in Chemical ToxicityR01GM034883 · NIGMS · UNIVERSITY OF PENNSYLVANIA · PI AVADHANI, NARAYAN G · 1985 to 2018
$6.1M
Metabolism of Carcinogens and Drugs by Human P450sR37CA090426 · NCI · VANDERBILT UNIVERSITY · PI GUENGERICH, F PETER · 2006 to 2015
$3.6M
NCI NIH HHS R37 CA090426NIGMS NIH HHS R01 GM034883NIGMS NIH HHS R01 GM34883
6 · The paper itself

Abstract

We report that polycyclic aromatic hydrocarbon (PAH)-inducible CYP1B1 is targeted to mitochondria by sequence-specific cleavage at the N terminus by a cytosolic Ser protease (polyserase 1) to activate the cryptic internal signal. Site-directed mutagenesis, COS-7 cell transfection, and in vitro import studies in isolated mitochondria showed that a positively charged domain at residues 41-48 of human CYP1B1 is part of the mitochondrial (mt) import signal. Ala scanning mutations showed that the Ser protease cleavage site resides between residues 37 and 41 of human CYP1B1. Benzo[a]pyrene (BaP) treatment induced oxidative stress, mitochondrial respiratory defects, and mtDNA damage that was attenuated by a CYP1B1-specific inhibitor, 2,3,4,5-tetramethoxystilbene. In support, the mitochondrial CYP1B1 supported by mitochondrial ferredoxin (adrenodoxin) and ferredoxin reductase showed high aryl hydrocarbon hydroxylase activity. Administration of benzo[a]pyrene or 2,3,7,8-tetrachlorodibenzodioxin induced similar mitochondrial functional abnormalities and oxidative stress in the lungs of wild-type mice and Cyp1a1/1a2-null mice, but the effects were markedly blunted in Cyp1b1-null mice. These results confirm a role for CYP1B1 in inducing PAH-mediated mitochondrial dysfunction. The role of mitochondrial CYP1B1 was assessed using A549 lung epithelial cells stably expressing shRNA against NADPH-cytochrome P450 oxidoreductase or mitochondrial adrenodoxin. Our results not only show conservation of the endoprotease cleavage mechanism for mitochondrial import of family 1 CYPs but also reveal a direct role for mitochondrial CYP1B1 in PAH-mediated oxidative and chemical damage to mitochondria.

Indexed as

Protein Sorting SignalsTeratogensAdrenodoxinAnimalsAryl Hydrocarbon HydroxylasesBenzo(a)pyreneCell Line, TumorChlorocebus aethiopsCOS CellsCytochrome P-450 CYP1B1FemaleHumansMaleMiceMice, KnockoutMitochondriaAdrenodoxinAryl Hydrocarbon HydroxylasesBenzo(a)pyreneCYP1B1 protein, humanCyp1b1 protein, mouseCytochrome P-450 CYP1B1Polychlorinated DibenzodioxinsProtein Sorting SignalsTeratogensCarcinogenesisCytochrome P450DNA DamageMembrane ProteinsMitochondriaMitochondrial DNA

Identifiers

PMID24497629
PMCPMC3975038
OpenAlexW1975833281

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.