The mitochondrial enzyme FAHD1 regulates complex II activity in breast cancer cells and is indispensable for basal BT-20 cells in vitro.


Journal

FEBS letters
ISSN: 1873-3468
Titre abrégé: FEBS Lett
Pays: England
ID NLM: 0155157

Informations de publication

Date de publication:
11 2022
Historique:
revised: 29 06 2022
received: 09 05 2022
accepted: 30 06 2022
pubmed: 14 8 2022
medline: 18 11 2022
entrez: 13 8 2022
Statut: ppublish

Résumé

The mitochondrial enzyme fumarylacetoacetate hydrolase domain-containing protein 1 (FAHD1) was identified to be upregulated in breast cancer tissues. Here, we show that FAHD1 is indispensable for the survival of BT-20 cells, representing the basal breast cancer cell type. A lentiviral knock-down of FAHD1 in the breast cancer cell lines MCF-7 and BT-20 results in lower succinate dehydrogenase (complex II) activity. In luminal MCF-7 cells, this leads to reduced proliferation when cultured in medium containing only glutamine as the carbon source. Of note, both cell lines show attenuated protein levels of the enzyme glutaminase (GLS) which activates programmed cell death in BT-20. These findings demonstrate that FAHD1 is crucial for the functionality of complex II in breast cancer cells and acts on glutaminolysis in the mitochondria.

Identifiants

pubmed: 35962472
doi: 10.1002/1873-3468.14462
pmc: PMC7613834
mid: EMS153221
doi:

Substances chimiques

Glutamine 0RH81L854J
Hydrolases EC 3.-

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

2781-2794

Subventions

Organisme : Austrian Science Fund FWF
ID : P 31582
Pays : Austria

Informations de copyright

© 2022 The Authors. FEBS Letters published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.

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Auteurs

Max Holzknecht (M)

Institute for Biomedical Aging Research, Leopold-Franzens University of Innsbruck, Austria.

Lena Guerrero-Navarro (L)

Institute for Biomedical Aging Research, Leopold-Franzens University of Innsbruck, Austria.

Michele Petit (M)

Institute for Biomedical Aging Research, Leopold-Franzens University of Innsbruck, Austria.

Eva Albertini (E)

Institute for Biomedical Aging Research, Leopold-Franzens University of Innsbruck, Austria.

Elisabeth Damisch (E)

Institute for Biomedical Aging Research, Leopold-Franzens University of Innsbruck, Austria.

Anna Simonini (A)

Institute for Biomedical Aging Research, Leopold-Franzens University of Innsbruck, Austria.

Fernando Schmitt (F)

Medical Faculty, CINTESIS@RISE (Health Research Network), Alameda Prof. Hernâni Monteiro, University of Porto, Portugal.

Walther Parson (W)

Institute of Legal Medicine, Medical University of Innsbruck, Austria.
Forensic Science Program, The Pennsylvania State University, University Park, PA, USA.

Heidelinde Fiegl (H)

Department of Obstetrics and Gynaecology, Medical University of Innsbruck, Austria.

Alexander Weiss (A)

Institute for Biomedical Aging Research, Leopold-Franzens University of Innsbruck, Austria.

Pidder Jansen-Duerr (P)

Institute for Biomedical Aging Research, Leopold-Franzens University of Innsbruck, Austria.

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