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

IF 3 4区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY
Max Holzknecht, Lena Guerrero-Navarro, Michele Petit, Eva Albertini, Elisabeth Damisch, Anna Simonini, Fernando Schmitt, Walther Parson, Heidelinde Fiegl, Alexander Weiss, Pidder Jansen-Duerr
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引用次数: 1

Abstract

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.

Abstract Image

Abstract Image

Abstract Image

线粒体酶FAHD1调节乳腺癌细胞中复合物II的活性,是体外基础BT-20细胞不可缺少的。
线粒体酶富马酰乙酸水解酶结构域蛋白1 (FAHD1)在乳腺癌组织中表达上调。在这里,我们发现FAHD1对于代表基底乳腺癌细胞类型的BT-20细胞的存活是必不可少的。慢病毒敲低乳腺癌细胞系MCF-7和BT-20中的FAHD1导致琥珀酸脱氢酶(复合物II)活性降低。在腔内MCF-7细胞中,在仅含谷氨酰胺作为碳源的培养基中培养时,这导致增殖降低。值得注意的是,这两种细胞系显示谷氨酰胺酶(GLS)的蛋白水平减弱,GLS可激活BT-20中的程序性细胞死亡。这些发现表明FAHD1对乳腺癌细胞复合体II的功能至关重要,并对线粒体中的谷氨酰胺水解起作用。
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来源期刊
FEBS Letters
FEBS Letters 生物-生化与分子生物学
CiteScore
6.60
自引率
2.90%
发文量
303
审稿时长
1 months
期刊介绍: FEBS Letters is one of the world''s leading journals in molecular biology and is renowned both for its quality of content and speed of production. Bringing together the most important developments in the molecular biosciences, FEBS Letters provides an international forum for Minireviews, Research Letters and Hypotheses that merit urgent publication.
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