Institute for Biomedical Aging Research, Leopold-Franzens University of Innsbruck, Austria.
Medical Faculty, CINTESIS@RISE (Health Research Network), Alameda Prof. Hernâni Monteiro, University of Porto, Portugal.
FEBS Lett. 2022 Nov;596(21):2781-2794. doi: 10.1002/1873-3468.14462. Epub 2022 Aug 12.
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.
线粒体酶琥珀酸乙酰乙酸水解酶结构域包含蛋白 1（FAHD1）在乳腺癌组织中被鉴定为上调。在这里，我们表明 FAHD1 对于基底乳腺癌细胞类型 BT-20 细胞的存活是必不可少的。在乳腺癌细胞系 MCF-7 和 BT-20 中，通过慢病毒敲低 FAHD1 导致琥珀酸脱氢酶（复合物 II）活性降低。在腔细胞 MCF-7 细胞中，当仅在含有谷氨酰胺作为碳源的培养基中培养时，这会导致增殖减少。值得注意的是，两种细胞系均显示出激活 BT-20 程序性细胞死亡的酶谷氨酰胺酶（GLS）的蛋白水平降低。这些发现表明 FAHD1 对于乳腺癌细胞中复合物 II 的功能至关重要，并作用于线粒体中的谷氨酰胺分解代谢。
