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

Autor: Holzknecht M; Institute for Biomedical Aging Research, Leopold-Franzens University of Innsbruck, Austria., Guerrero-Navarro L; Institute for Biomedical Aging Research, Leopold-Franzens University of Innsbruck, Austria., Petit M; Institute for Biomedical Aging Research, Leopold-Franzens University of Innsbruck, Austria., Albertini E; Institute for Biomedical Aging Research, Leopold-Franzens University of Innsbruck, Austria., Damisch E; Institute for Biomedical Aging Research, Leopold-Franzens University of Innsbruck, Austria., Simonini A; Institute for Biomedical Aging Research, Leopold-Franzens University of Innsbruck, Austria., Schmitt F; Medical Faculty, CINTESIS@RISE (Health Research Network), Alameda Prof. Hernâni Monteiro, University of Porto, Portugal., Parson W; Institute of Legal Medicine, Medical University of Innsbruck, Austria.; Forensic Science Program, The Pennsylvania State University, University Park, PA, USA., Fiegl H; Department of Obstetrics and Gynaecology, Medical University of Innsbruck, Austria., Weiss A; Institute for Biomedical Aging Research, Leopold-Franzens University of Innsbruck, Austria., Jansen-Duerr P; Institute for Biomedical Aging Research, Leopold-Franzens University of Innsbruck, Austria.
Jazyk: angličtina
Zdroj: FEBS letters [FEBS Lett] 2022 Nov; Vol. 596 (21), pp. 2781-2794. Date of Electronic Publication: 2022 Aug 12.
DOI: 10.1002/1873-3468.14462
Abstrakt: 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.
(© 2022 The Authors. FEBS Letters published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)
Databáze: MEDLINE
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