Evidence map›Paper›PMID 34520742›Full record

ArticleCell chemical biology2022

FADS2-dependent fatty acid desaturation dictates cellular sensitivity to ferroptosis and permissiveness for hepatitis C virus replication.

Daisuke Yamane, Yuri Hayashi, Moe Matsumoto, Hiroki Nakanishi, Haruka Imagawa, Michinori Kohara, Stanley M Lemon, Ikuyo Ichi

Open access · greenAbstract read
In one paragraph

Article in Cell chemical biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 98 papers.

0numbers the graph read from it
0cells of the map it votes in
98citing papers in PubMed
13.2field-weighted citation impact, top 1% 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

98 citing papers in PubMed, 141 citations in OpenAlex.

  1. Review
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  9. Plasma Linoleic Acid Is Associated With Pediatric Sepsis Phenotype and Acute Kidney Injury.Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies · 2026
    Article
  10. Article
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  12. Review
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  15. Recent progress in understanding ferroptosis mechanisms in infectious diseases.Frontiers in cellular and infection microbiology · 2026
    Review
  16. Article
  17. Review
  18. Article
  19. Review
  20. Review

38 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

8 authors at 4 institutions in 2 countries.

Daisuke YamaneDepartment of Diseases and Infection, Tokyo Metropolitan Institute of Medical Science, Setagaya-ku, Tokyo 156-8506, Japan. Electronic address: yamane-ds@igakuken.or.jp.
Yuri HayashiGraduate School of Humanities and Sciences, Ochanomizu University, Bunkyō-ku, Tokyo 112-8610, Japan.
Moe MatsumotoDepartment of Diseases and Infection, Tokyo Metropolitan Institute of Medical Science, Setagaya-ku, Tokyo 156-8506, Japan.
Hiroki NakanishiResearch Center for Biosignaling, Akita University, Akita-city, Akita 010-8543, Japan; Lipidome Lab Co., Ltd, Akita-city, Akita 010-0825, Japan.
Haruka ImagawaLipidome Lab Co., Ltd, Akita-city, Akita 010-0825, Japan.
Michinori KoharaDepartment of Diseases and Infection, Tokyo Metropolitan Institute of Medical Science, Setagaya-ku, Tokyo 156-8506, Japan.
Stanley M LemonLineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7292, USA; Departments of Medicine and Microbiology & Immunology, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7292, USA.
Ikuyo IchiNatural Science Division, Ochanomizu University, Bunkyō-ku, Tokyo 112-8610, Japan; Institute for Human Life Innovation, Faculty of Core Research, Ochanomizu University, Bunkyō-ku, Tokyo 112-8610, Japan.
Tokyo Metropolitan Institute of Medical Science · JPOchanomizu University · JPAkita University · JPUniversity of North Carolina at Chapel Hill · US

Funding

Micro-RNA 122 and Chronic Hepatitis CR01AI095690 · NIAID · UNIV OF NORTH CAROLINA CHAPEL HILL · PI LEMON, STANLEY M. · 2011 to 2020
$3.7M
NIAID NIH HHS R01 AI095690
6 · The paper itself

Abstract

The metabolic oxidative degradation of cellular lipids severely restricts replication of hepatitis C virus (HCV), a leading cause of chronic liver disease, but little is known about the factors regulating this process in infected cells. Here we show that HCV is restricted by an iron-dependent mechanism resembling the one triggering ferroptosis, an iron-dependent form of non-apoptotic cell death, and mediated by the non-canonical desaturation of oleate to Mead acid and other highly unsaturated fatty acids by fatty acid desaturase 2 (FADS2). Genetic depletion and ectopic expression experiments show FADS2 is a key determinant of cellular sensitivity to ferroptosis. Inhibiting FADS2 markedly enhances HCV replication, whereas the ferroptosis-inducing compound erastin alters conformation of the HCV replicase and sensitizes it to direct-acting antiviral agents targeting the viral protease. Our results identify FADS2 as a rate-limiting factor in ferroptosis, and suggest the possibility of pharmacologically manipulating the ferroptosis pathway to attenuate viral replication.

Indexed as

FerroptosisHepatitis C, ChronicAntiviral AgentsFatty Acid DesaturasesFatty Acids, UnsaturatedHepacivirusHumansIronPermissivenessVirus ReplicationAntiviral AgentsFADS2 protein, humanFatty Acid DesaturasesFatty Acids, UnsaturatedIrondirect-acting antiviralsFADS2ferroptosishepatitis C viruslipid peroxidationMead acidpolyunsaturated fatty acid

Identifiers

PMID34520742
PMCPMC8913804
OpenAlexW3201476493

What OpenQuestion holds

Textmetadata
LicenceTDM
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.