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The mitochondrial enzyme FAHD1 regulates complex II activity in breast cancer cells and is indispensable for basal BT ‐20 cells in vitro
Author(s) -
Holzknecht Max,
GuerreroNavarro Lena,
Petit Michele,
Albertini Eva,
Damisch Elisabeth,
Simonini Anna,
Schmitt Fernando,
Parson Walther,
Fiegl Heidelinde,
Weiss Alexander,
JansenDuerr Pidder
Publication year - 2022
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1002/1873-3468.14462
Subject(s) - glutaminolysis , cancer cell , glutaminase , glutamine , mitochondrion , cell culture , apoptosis , enzyme , chemistry , biology , biochemistry , microbiology and biotechnology , cancer , amino acid , genetics
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.