Evidence map›Paper›PMID 30540494›Full record

ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2019

Peroxisomes can oxidize medium- and long-chain fatty acids through a pathway involving ABCD3 and HSD17B4.

Sara Violante, Nihad Achetib, Carlo W T van Roermund, Jacob Hagen, Tetyana Dodatko, Frédéric M Vaz, Hans R Waterham, Hongjie Chen, Myriam Baes, Chunli Yu and 2 more

Open access · greenAbstract read
In one paragraph

Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 86 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
86citing papers in PubMed, 2 pooled it
3.5field-weighted citation impact, top 6% 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

86 citing papers in PubMed, 2 syntheses or guidelines pooled it, 138 citations in OpenAlex.

  1. Pooled it
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  14. Odd-Chain Dicarboxylic Acid Feeding Produces a Glutaric Aciduria Type 1-Like Metabolic Signature in Mice.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025
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  19. Measuring renal cortical cell-specific mitochondrial metabolism.bioRxiv : the preprint server for biology · 2025
    Article
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26 more citing papers are in PubMed but not listed here.

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

12 authors at 4 institutions in 3 countries.

Sara ViolanteDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Nihad AchetibDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Carlo W T van RoermundDepartment of Clinical Chemistry, Amsterdam, The Netherlands.
Jacob HagenDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Tetyana DodatkoDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Frédéric M VazDepartment of Clinical Chemistry, Amsterdam, The Netherlands.
Hans R WaterhamDepartment of Clinical Chemistry, Amsterdam, The Netherlands.
Hongjie ChenDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Myriam BaesLaboratory of Cell Metabolism, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven-University of Leuven, Leuven, Belgium.
Chunli YuDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Carmen A ArgmannDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Sander M HoutenDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Icahn School of Medicine at Mount Sinai · USAcademic Medical Center · NLKU Leuven · BEUniversity of Amsterdam · NL

Funding

Novel pathophysiological insights into mitochondrial fatty acid oxidation disordersR01DK113172 · NIDDK · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI HOUTEN, SANDER MICHEL · 2017 to 2020
$2.1M
NIDDK NIH HHS R01 DK113172
6 · The paper itself

Abstract

Peroxisomes are essential organelles for the specialized oxidation of a wide variety of fatty acids, but they are also able to degrade fatty acids that are typically handled by mitochondria. Using a combination of pharmacological inhibition and clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR associated protein 9 genome editing technology to simultaneously manipulate peroxisomal and mitochondrial fatty acid β-oxidation (FAO) in HEK-293 cells, we identified essential players in the metabolic crosstalk between these organelles. Depletion of carnitine palmitoyltransferase (CPT)2 activity through pharmacological inhibition or knockout (KO) uncovered a significant residual peroxisomal oxidation of lauric and palmitic acid, leading to the production of peroxisomal acylcarnitine intermediates. Generation and analysis of additional single- and double-KO cell lines revealed that the D-bifunctional protein (HSD17B4) and the peroxisomal ABC transporter ABCD3 are essential in peroxisomal oxidation of lauric and palmitic acid. Our results indicate that peroxisomes not only accept acyl-CoAs but can also oxidize acylcarnitines in a similar biochemical pathway. By using an Hsd17b4 KO mouse model, we demonstrated that peroxisomes contribute to the plasma acylcarnitine profile after acute inhibition of CPT2, proving in vivo relevance of this pathway. We summarize that peroxisomal FAO is important when mitochondrial FAO is defective or overloaded.-Violante, S., Achetib, N., van Roermund, C. W. T., Hagen, J., Dodatko, T., Vaz, F. M., Waterham, H. R., Chen, H., Baes, M., Yu, C., Argmann, C. A., Houten, S. M. Peroxisomes can oxidize medium- and long-chain fatty acids through a pathway involving ABCD3 and HSD17B4.

Indexed as

AnimalsATP-Binding Cassette TransportersCarnitineCarnitine O-PalmitoyltransferaseCRISPR-Cas SystemsFatty AcidsHEK293 CellsHumansLauric AcidsMembrane ProteinsMiceMice, KnockoutMitochondriaOxidation-ReductionPalmitic AcidPeroxisomal Bifunctional EnzymeABCD3 protein, humanAbcd3 protein, mouseacylcarnitineATP-Binding Cassette TransportersCarnitineCarnitine O-PalmitoyltransferaseEhhadh protein, mouseFatty AcidsHSD17B4 protein, humanHsd17b4 protein, mouselauric acidLauric AcidsMembrane ProteinsPalmitic AcidPeroxisomal Bifunctional EnzymePeroxisomal Multifunctional Protein-2Recombinant ProteinsacylcarnitineCPT2 deficiencyfatty acid oxidationmitochondriaorganellar crosstalk

Identifiers

PMID30540494
PMCPMC6404569
OpenAlexW2904375134

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.