Evidence map›Paper›PMID 33916579›Full record

ArticleCancers2021

Biochemical Background in Mitochondria Affects 2HG Production by IDH2 and ADHFE1 in Breast Carcinoma.

Jitka Špačková, Klára Gotvaldová, Aleš Dvořák, Alexandra Urbančoková, Kateřina Pospíšilová, David Větvička, Alberto Leguina-Ruzzi, Petra Tesařová, Libor Vítek, Petr Ježek and 1 more

Open access · goldAbstract read
In one paragraph

Article in Cancers, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
1.0field-weighted citation impact, top 30% 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

5 citing papers in PubMed, 11 citations in OpenAlex.

  1. Review
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  5. Review
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

11 authors at 3 institutions in 1 country.

Jitka ŠpačkováInstitute of Physiology of the Czech Academy of Sciences, Laboratory of Mitochondrial Physiology, 142 20 Prague, Czech Republic.
Klára GotvaldováInstitute of Physiology of the Czech Academy of Sciences, Laboratory of Mitochondrial Physiology, 142 20 Prague, Czech Republic.ORCID 0000-0002-0774-4454
Aleš DvořákInstitute of Physiology of the Czech Academy of Sciences, Laboratory of Mitochondrial Physiology, 142 20 Prague, Czech Republic.ORCID 0000-0002-1285-6928
Alexandra UrbančokováInstitute of Physiology of the Czech Academy of Sciences, Laboratory of Mitochondrial Physiology, 142 20 Prague, Czech Republic.
Kateřina PospíšilováInstitute of Medical Biochemistry and Laboratory Diagnostics of the General University Hospital and the First Faculty of Medicine, Charles University, 121 08 Prague, Czech Republic.
David VětvičkaInstitute of Biophysics and Informatics, the First Faculty of Medicine, Charles University, 120 00 Prague, Czech Republic.
Alberto Leguina-RuzziInstitute of Physiology of the Czech Academy of Sciences, Laboratory of Mitochondrial Physiology, 142 20 Prague, Czech Republic.ORCID 0000-0002-4761-3491
Petra TesařováDepartment of Oncology, the General University Hospital and The First Faculty of Medicine, 128 08 Prague, Czech Republic.ORCID 0000-0003-3607-3474
Libor VítekInstitute of Medical Biochemistry and Laboratory Diagnostics of the General University Hospital and the First Faculty of Medicine, Charles University, 121 08 Prague, Czech Republic.ORCID 0000-0002-5318-0151
Petr JežekInstitute of Physiology of the Czech Academy of Sciences, Laboratory of Mitochondrial Physiology, 142 20 Prague, Czech Republic.ORCID 0000-0002-2720-9395
Katarína SmolkováInstitute of Physiology of the Czech Academy of Sciences, Laboratory of Mitochondrial Physiology, 142 20 Prague, Czech Republic.ORCID 0000-0002-4734-0200
Czech Academy of Sciences · CZCharles University · CZGeneral University Hospital in Prague · CZ

Funding

Grantová Agentura České Republiky 21-01205S
6 · The paper itself

Abstract

Mitochondrial production of 2-hydroxyglutarate (2HG) can be catalyzed by wild-type isocitrate dehydrogenase 2 (IDH2) and alcohol dehydrogenase, iron-containing 1 (ADHFE1). We investigated whether biochemical background and substrate concentration in breast cancer cells promote 2HG production. To estimate its role in 2HG production, we quantified 2HG levels and its enantiomers in breast cancer cells using analytical approaches for metabolomics. By manipulation of mitochondrial substrate fluxes using genetic and pharmacological approaches, we demonstrated the existence of active competition between 2HG producing enzymes, i.e., IDH2 and ADHFE1. Moreover, we showed that distinct fractions of IDH2 enzyme molecules operate in distinct oxido-reductive modes, providing NADPH and producing 2HG simultaneously. We have also detected 2HG release in the urine of breast cancer patients undergoing adjuvant therapy and detected a correlation with stages of breast carcinoma development. In summary, we provide a background for vital mitochondrial production of 2HG in breast cancer cells with outcomes towards cancer biology and possible future diagnosis of breast carcinoma.

Indexed as

2HGbreast carcinomaIDH2

Identifiers

PMID33916579
PMCPMC8038481
OpenAlexW3134523315

What OpenQuestion holds

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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.