Mitochondrial enzyme FAHD1 reduces ROS in osteosarcoma.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
22 Apr 2024
22 Apr 2024
Historique:
received:
20
08
2023
accepted:
17
04
2024
medline:
23
4
2024
pubmed:
23
4
2024
entrez:
22
4
2024
Statut:
epublish
Résumé
This study investigated the impact of overexpressing the mitochondrial enzyme Fumarylacetoacetate hydrolase domain-containing protein 1 (FAHD1) in human osteosarcoma epithelial cells (U2OS) in vitro. While the downregulation or knockdown of FAHD1 has been extensively researched in various cell types, this study aimed to pioneer the exploration of how increased catalytic activity of human FAHD1 isoform 1 (hFAHD1.1) affects human cell metabolism. Our hypothesis posited that elevation in FAHD1 activity would lead to depletion of mitochondrial oxaloacetate levels. This depletion could potentially result in a decrease in the flux of the tricarboxylic acid (TCA) cycle, thereby accompanied by reduced ROS production. In addition to hFAHD1.1 overexpression, stable U2OS cell lines were established overexpressing a catalytically enhanced variant (T192S) and a loss-of-function variant (K123A) of hFAHD1. It is noteworthy that homologs of the T192S variant are present in animals exhibiting increased resistance to oxidative stress and cancer. Our findings demonstrate that heightened activity of the mitochondrial enzyme FAHD1 decreases cellular ROS levels in U2OS cells. However, these results also prompt a series of intriguing questions regarding the potential role of FAHD1 in mitochondrial metabolism and cellular development.
Identifiants
pubmed: 38649439
doi: 10.1038/s41598-024-60012-x
pii: 10.1038/s41598-024-60012-x
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
9231Informations de copyright
© 2024. The Author(s).
Références
Sun, W. et al. Metabolism of reactive oxygen species in osteosarcoma and potential treatment applications. Cells 9, 87 (2019).
pubmed: 31905813
pmcid: 7017125
doi: 10.3390/cells9010087
Kirtonia, A., Sethi, G. & Garg, M. The multifaceted role of reactive oxygen species in tumorigenesis. Cell. Mol. Life Sci. 77, 4459–4483 (2020).
pubmed: 32358622
doi: 10.1007/s00018-020-03536-5
Oka, N. et al. Ascorbate sensitizes human osteosarcoma cells to the cytostatic effects of cisplatin. Pharmacol. Res. Perspect. 8, e00632 (2020).
pubmed: 32725721
pmcid: 7387887
doi: 10.1002/prp2.632
Satheesh, N. J., Samuel, S. M. & Büsselberg, D. Combination therapy with vitamin C could eradicate cancer stem cells. Biomolecules 10, 79 (2020).
pubmed: 31947879
pmcid: 7022456
doi: 10.3390/biom10010079
Jaquet, V., Scapozza, L., Clark, R. A., Krause, K.-H. & Lambeth, J. D. Small-molecule NOX inhibitors: ROS-generating NADPH oxidases as therapeutic targets. Antioxid. Redox Signal. 11, 2535–2552 (2009).
pubmed: 19309261
doi: 10.1089/ars.2009.2585
Nathan, F. M., Singh, V. A., Dhanoa, A. & Palanisamy, U. D. Oxidative stress and antioxidant status in primary bone and soft tissue sarcoma. BMC Cancer 11, 382 (2011).
pubmed: 21871117
pmcid: 3178545
doi: 10.1186/1471-2407-11-382
Kamijo, A., Koshino, T., Uesugi, M., Nitto, H. & Saito, T. Inhibition of lung metastasis of osteosarcoma cell line POS-1 transplanted into mice by thigh ligation. Cancer Lett. 188, 213–219 (2002).
pubmed: 12406567
doi: 10.1016/S0304-3835(02)00433-0
Park, J.-Y., Kim, Y. W. & Park, Y.-K. Nrf2 expression is associated with poor outcome in osteosarcoma. Pathology 44, 617–621 (2012).
pubmed: 23172081
doi: 10.1097/PAT.0b013e328359d54b
Liu, W. et al. TRIM22 inhibits osteosarcoma progression through destabilizing NRF2 and thus activation of ROS/AMPK/mTOR/autophagy signaling. Redox Biol. 53, 102344 (2022).
pubmed: 35636015
pmcid: 9144049
doi: 10.1016/j.redox.2022.102344
Gong, T., Su, X., Xia, Q., Wang, J. & Kan, S. Expression of NF-κB and PTEN in osteosarcoma and its clinical significance. Oncol. Lett. 14, 6744–6748 (2017).
pubmed: 29151913
pmcid: 5678349
Pircher, H. et al. Identification of FAH domain-containing protein 1 (FAHD1) as oxaloacetate decarboxylase. J. Biol. Chem. 290, 6755–6762 (2015).
pubmed: 25575590
pmcid: 4358102
doi: 10.1074/jbc.M114.609305
Weiss, A. K. H. et al. Inhibitors of fumarylacetoacetate hydrolase domain containing protein 1 (FAHD1). Molecules (Basel, Switzerland) 26, 5009 (2021).
pubmed: 34443596
doi: 10.3390/molecules26165009
Weiss, A. K. H. et al. Structural basis for the bi-functionality of human oxaloacetate decarboxylase FAHD1. Biochem. J. 475, 3561–3576 (2018).
pubmed: 30348641
doi: 10.1042/BCJ20180750
Etemad, S. et al. Oxaloacetate decarboxylase FAHD1 – a new regulator of mitochondrial function and senescence. Mech. Age. Dev. 177, 22–29 (2019).
doi: 10.1016/j.mad.2018.07.007
Weiss, A. K. H. et al. Regulation of cellular senescence by eukaryotic members of the FAH superfamily – A role in calcium homeostasis?. Mech. Age. Dev. 190, 111284 (2020).
doi: 10.1016/j.mad.2020.111284
Weiss, A. K. H. H., Loeffler, J. R., Liedl, K. R., Gstach, H. & Jansen-Dürr, P. The fumarylacetoacetate hydrolase (FAH) superfamily of enzymes: multifunctional enzymes from microbes to mitochondria. Biochem. Soc. Trans. 46, 295–309 (2018).
pubmed: 29487229
doi: 10.1042/BST20170518
Hong, H., Seo, H., Park, W. & Kim, K.K.-J. Sequence, structure and function-based classification of the broadly conserved FAH superfamily reveals two distinct fumarylpyruvate hydrolase subfamilies. Environ. Microbial. 22, 270–285 (2020).
doi: 10.1111/1462-2920.14844
Jansen-Duerr, P., Pircher, H. & Weiss, A. K. H. The FAH fold meets the krebs cycle. Mol. Enzymol. Drug Targets 02, 1–5 (2016).
Montal, E. D. et al. PEPCK coordinates the regulation of central carbon metabolism to promote cancer cell growth. Molecular cell 60, 571–583 (2015).
pubmed: 26481663
pmcid: 4656111
doi: 10.1016/j.molcel.2015.09.025
Gebregiworgis, T. et al. Glucose limitation alters glutamine metabolism in MUC1-overexpressing pancreatic cancer cells. J. Proteome Res. 16, 3536–3546 (2017).
pubmed: 28809118
pmcid: 5634392
doi: 10.1021/acs.jproteome.7b00246
Yang, C. et al. Glutamine oxidation maintains the TCA cycle and cell survival during impaired mitochondrial pyruvate transport. Mol. Cell 56, 414–424 (2014).
pubmed: 25458842
pmcid: 4268166
doi: 10.1016/j.molcel.2014.09.025
Holzknecht, M. et al. The mitochondrial enzyme FAHD1 regulates complex II activity in breast cancer cells and is indispensable for basal BT-20 cells in vitro. FEBS Lett. 596, 2781–2794 (2022).
pubmed: 35962472
pmcid: 7613834
doi: 10.1002/1873-3468.14462
Petit, M., Koziel, R., Etemad, S., Pircher, H. & Jansen-Dürr, P. Depletion of oxaloacetate decarboxylase FAHD1 inhibits mitochondrial electron transport and induces cellular senescence in human endothelial cells. Exper. Gerontol. 92, 7–12 (2017).
doi: 10.1016/j.exger.2017.03.004
Taferner, A. et al. fah domain containing protein 1 (FAHD-1) is required for mitochondrial function and locomotion activity in C. elegans. PLOS ONE 10, e0134161 (2015).
pubmed: 26266933
pmcid: 4534308
doi: 10.1371/journal.pone.0134161
Baraldo, G., Etemad, S., Weiss, A. K. H., Jansen-Dürr, P. & Mack, H. I. D. Modulation of serotonin signaling by the putative oxaloacetate decarboxylase FAHD-1 in Caenorhabditis elegans. PLOS ONE 14, e0220434 (2019).
pubmed: 31412049
pmcid: 6693844
doi: 10.1371/journal.pone.0220434
Pircher, H. et al. Identification of human fumarylacetoacetate hydrolase domain-containing protein 1 (FAHD1) as a novel mitochondrial acylpyruvase. J. Biol. Chem. 286, 36500–36508 (2011).
pubmed: 21878618
pmcid: 3196145
doi: 10.1074/jbc.M111.264770
Tang, X. et al. A method for high transfection efficiency in THP-1 suspension cells without PMA treatment. Anal. Biochem. 544, 93–97 (2018).
pubmed: 29305095
doi: 10.1016/j.ab.2017.12.032
Fritsche-Guenther, R. et al. Progression-dependent altered metabolism in osteosarcoma resulting in different nutrient source dependencies. Cancers 12, 1371 (2020).
pubmed: 32471029
pmcid: 7352851
doi: 10.3390/cancers12061371
Sheng, G., Gao, Y., Yang, Y. & Wu, H. Osteosarcoma and Metastasis. Front. Oncol. 11, 780264 (2021).
pubmed: 34956899
pmcid: 8702962
doi: 10.3389/fonc.2021.780264
Shen, S. et al. CircECE1 activates energy metabolism in osteosarcoma by stabilizing c-Myc. Mol. Cancer 19, 151 (2020).
pubmed: 33106166
pmcid: 7586679
doi: 10.1186/s12943-020-01269-4
Leite, T. C., Watters, R. J., Weiss, K. R. & Intini, G. Avenues of research in dietary interventions to target tumor metabolism in osteosarcoma. J. Transl. Med. 19, 450 (2021).
pubmed: 34715874
pmcid: 8555297
doi: 10.1186/s12967-021-03122-8
Feng, Z., Ou, Y. & Hao, L. The roles of glycolysis in osteosarcoma. Front. Pharmacol. 13, 950886 (2022).
pubmed: 36059961
pmcid: 9428632
doi: 10.3389/fphar.2022.950886
Gray, A., Dang, B. N., Moore, T. B., Clemens, R. & Pressman, P. A review of nutrition and dietary interventions in oncology. SAGE Open Med. 8, 2050312120926877 (2020).
pubmed: 32537159
pmcid: 7268120
doi: 10.1177/2050312120926877
Chen, J. et al. essential role of nonessential amino acid glutamine in atherosclerotic cardiovascular disease. DNA Cell Biol. 39, 8–15 (2020).
pubmed: 31825254
doi: 10.1089/dna.2019.5034
Jiménez, J. A., Lawlor, E. R. & Lyssiotis, C. A. Amino acid metabolism in primary bone sarcomas. Front. Oncol. 12, 1001318 (2022).
pubmed: 36276057
pmcid: 9581121
doi: 10.3389/fonc.2022.1001318
Jin, J., Byun, J.-K., Choi, Y.-K. & Park, K.-G. Targeting glutamine metabolism as a therapeutic strategy for cancer. Exper. Mol. Med. 55, 706–715 (2023).
doi: 10.1038/s12276-023-00971-9
Wu, S. et al. Targeting glutamine dependence through GLS1 inhibition suppresses ARID1A-inactivated clear cell ovarian carcinoma. Nat. Cancer 2, 189–200 (2021).
pubmed: 34085048
pmcid: 8168620
doi: 10.1038/s43018-020-00160-x
Hettmer, S. et al. Functional genomic screening reveals asparagine dependence as a metabolic vulnerability in sarcoma. eLife 4, e09436 (2015).
pubmed: 26499495
pmcid: 4695385
doi: 10.7554/eLife.09436
Krömer, J. O., Sorgenfrei, O., Klopprogge, K., Heinzle, E. & Wittmann, C. In-depth profiling of lysine-producing Corynebacterium glutamicum by combined analysis of the transcriptome, metabolome, and fluxome. J. Bacteriol. 186, 1769–1784 (2004).
pubmed: 14996808
pmcid: 355958
doi: 10.1128/JB.186.6.1769-1784.2004
Ran, T., Wang, Y., Xu, D. & Wang, W. Expression, purification, crystallization and preliminary crystallographic analysis of Cg1458: A novel oxaloacetate decarboxylase from Corynebacterium glutamicum. Acta Crystallographica Section F 67, 968–970 (2011).
Ran, T. et al. Crystal structures of Cg1458 reveal a catalytic lid domain and a common catalytic mechanism for the FAH family. Biochem. J. 449, 51–60 (2012).
doi: 10.1042/BJ20120913
Hutter, E. et al. Senescence-associated changes in respiration and oxidative phosphorylation in primary human fibroblasts. Biochem. J. 380, 919–928 (2004).
pubmed: 15018610
pmcid: 1224220
doi: 10.1042/bj20040095
Fang, X. et al. Adaptations to a subterranean environment and longevity revealed by the analysis of mole rat genomes. Cell Rep. 8, 1354–1364 (2014).
pubmed: 25176646
pmcid: 4350764
doi: 10.1016/j.celrep.2014.07.030
Vleck, C. M., Haussmann, M. F. & Vleck, D. Avian senescence: underlying mechanisms. J. Ornithol. 148, 611–624 (2007).
doi: 10.1007/s10336-007-0186-5
Hoekstra, L. A., Schwartz, T. S., Sparkman, A. M., Miller, D. A. W. & Bronikowski, A. M. The untapped potential of reptile biodiversity for understanding how and why animals age. Funct. Ecol. 34, 38–54 (2020).
pubmed: 32921868
doi: 10.1111/1365-2435.13450
Coincon, M., Wang, W., Sygusch, J. & Seah, S. Y. K. Crystal structure of reaction intermediates in pyruvate class II aldolase: Substrate cleavage, enolate stabilization, and substrate specificity. J. Biol. Chem. 287, 36208–36221 (2012).
pubmed: 22908224
pmcid: 3476288
doi: 10.1074/jbc.M112.400705
Koendjbiharie, J. G., van Kranenburg, R. & Kengen, S. W. M. The PEP-pyruvate-oxaloacetate node: Variation at the heart of metabolism. FEMS Microbiol. Rev. 45, fuaa061 (2021).
pubmed: 33289792
doi: 10.1093/femsre/fuaa061
Sauer, U. & Eikmanns, B. J. The PEP-pyruvate-oxaloacetate node as the switch point for carbon flux distribution in bacteria. FEMS Microbiol. Rev. 29, 765–794 (2005).
pubmed: 16102602
doi: 10.1016/j.femsre.2004.11.002
Lee, W.-C., Ji, X., Nissim, I. & Long, F. Malic enzyme couples mitochondria with aerobic glycolysis in osteoblasts. Cell Rep. 32, 108108 (2020).
pubmed: 32905773
pmcid: 8183612
doi: 10.1016/j.celrep.2020.108108
Woyda-Ploszczyca, A. M. & Jarmuszkiewicz, W. Different effects of guanine nucleotides (GDP and GTP) on protein-mediated mitochondrial proton leak. PloS one 9, e98969 (2014).
pubmed: 24904988
pmcid: 4056835
doi: 10.1371/journal.pone.0098969
Simmen, F. A., Alhallak, I. & Simmen, R. C. M. Malic enzyme 1 (ME1) in the biology of cancer: it is not just intermediary metabolism. J. Mol. Endocrinol. 65, R77–R90 (2020).
pubmed: 33064660
pmcid: 7577320
doi: 10.1530/JME-20-0176
Weiher, H. et al. A monoclonal antibody raised against bacterially expressed MPV17 sequences shows peroxisomal, endosomal and lysosomal localisation in U2OS cells. BMC Res. Notes 9, 128 (2016).
pubmed: 26921094
pmcid: 4769525
doi: 10.1186/s13104-016-1939-0
Guzmán, C., Bagga, M., Kaur, A., Westermarck, J. & Abankwa, D. ColonyArea: An ImageJ plugin to automatically quantify colony formation in clonogenic assays. PLoS ONE 9, e92444 (2014).
pubmed: 24647355
pmcid: 3960247
doi: 10.1371/journal.pone.0092444
Murphy, M. P. et al. Guidelines for measuring reactive oxygen species and oxidative damage in cells and in vivo. Nat. Metabolism 4, 651–662 (2022).
doi: 10.1038/s42255-022-00591-z
Rao, X., Huang, X., Zhou, Z. & Lin, X. An improvement of the 2ˆ(-delta delta CT) method for quantitative real-time polymerase chain reaction data analysis. Biostat. Bioinf. Biomath. 3, 71–85 (2013).
Weglarz-Tomczak, E., Rijlaarsdam, D. J., Tomczak, J. M. & Brul, S. GEM-based metabolic profiling for human bone osteosarcoma under different glucose and glutamine availability. Int. J. Mol. Sci. 22, 1470 (2021).
pubmed: 33540580
pmcid: 7867237
doi: 10.3390/ijms22031470
Bodineau, C. et al. Two parallel pathways connect glutamine metabolism and mTORC1 activity to regulate glutamoptosis. Nat. Commun. 12, 4814 (2021).
pubmed: 34376668
pmcid: 8355106
doi: 10.1038/s41467-021-25079-4
Lee, C. M., Lee, J., Nam, M. J. & Park, S.-H. Indole-3-carbinol induces apoptosis in human osteosarcoma MG-63 and U2OS cells. BioMed Res. Int. 2018, 7970618 (2018).
pubmed: 30627573
pmcid: 6304504
doi: 10.1155/2018/7970618
Mund, A. et al. Deep visual proteomics defines single-cell identity and heterogeneity. Nat. Biotechnol. 40, 1231–1240 (2022).
pubmed: 35590073
pmcid: 9371970
doi: 10.1038/s41587-022-01302-5
Smolková, K. & Ježek, P. The role of mitochondrial NADPH-dependent isocitrate dehydrogenase in cancer cells. Int. J. Cell Biol. 2012, 1–12 (2012).
doi: 10.1155/2012/273947
Covarrubias, A. J., Perrone, R., Grozio, A. & Verdin, E. NAD+ metabolism and its roles in cellular processes during ageing Nature reviews. Mol. Cell Biol. 22, 119–141 (2021).
Arnold, P. K. et al. A non-canonical tricarboxylic acid cycle underlies cellular identity. Nature 603, 477–481 (2022).
pubmed: 35264789
pmcid: 8934290
doi: 10.1038/s41586-022-04475-w
Han, T. et al. How does cancer cell metabolism affect tumor migration and invasion?. Cell Adhesion & Migration 7, 395–403 (2013).
doi: 10.4161/cam.26345
Xiang, L. et al. Glutaminase 1 expression in colorectal cancer cells is induced by hypoxia and required for tumor growth, invasion, and metastatic colonization. Cell Death Dis. 10, 40 (2019).
pubmed: 30674873
pmcid: 6426853
doi: 10.1038/s41419-018-1291-5