@article{lodge_scheidemantle_adams_cottam_richard_breuer_thompson_shrestha_liu_kennedy_2024, title={Fructose regulates the pentose phosphate pathway and induces an inflammatory and resolution phenotype in Kupffer cells}, volume={14}, ISSN={["2045-2322"]}, DOI={10.1038/s41598-024-54272-w}, abstractNote={Abstract}, number={1}, journal={SCIENTIFIC REPORTS}, author={Lodge, Mareca and Scheidemantle, Grace and Adams, Victoria R. and Cottam, Matthew A. and Richard, Daniel and Breuer, Denitra and Thompson, Peter and Shrestha, Kritika and Liu, Xiaojing and Kennedy, Arion}, year={2024}, month={Feb} } @article{adams_collins_williams_holmes_hess_atkins_scheidemantle_liu_lodge_johnson_et al._2024, title={Myeloid cell MHC I expression drives CD8+ T cell activation in nonalcoholic steatohepatitis}, volume={14}, ISSN={["1664-3224"]}, url={https://doi.org/10.3389/fimmu.2023.1302006}, DOI={10.3389/fimmu.2023.1302006}, abstractNote={Background & aimsActivated CD8+ T cells are elevated in Nonalcoholic steatohepatitis (NASH) and are important for driving fibrosis and inflammation. Despite this, mechanisms of CD8+ T cell activation in NASH are largely limited. Specific CD8+ T cell subsets may become activated through metabolic signals or cytokines. However, studies in NASH have not evaluated the impact of antigen presentation or the involvement of specific antigens. Therefore, we determined if activated CD8+ T cells are dependent on MHC class I expression in NASH to regulate fibrosis and inflammation.}, journal={FRONTIERS IN IMMUNOLOGY}, author={Adams, Victoria R. and Collins, Leonard B. and Williams, Taufika Islam and Holmes, Jennifer and Hess, Paul and Atkins, Hannah M. and Scheidemantle, Grace and Liu, Xiaojing and Lodge, Mareca and Johnson, Aaron J. and et al.}, editor={Williams, Taufika Islam and Collins, Leonard B. and Kennedy, ArionEditors}, year={2024}, month={Jan} } @article{zhang_fang_xie_carrico_meyer_wei_bons_rose_riley_kwok_et al._2024, title={Regulation of urea cycle by reversible high-stoichiometry lysine succinylation}, ISSN={["2522-5812"]}, DOI={10.1038/s42255-024-01005-y}, journal={NATURE METABOLISM}, author={Zhang, Ran and Fang, Jingqi and Xie, Xueshu and Carrico, Chris and Meyer, Jesse G. and Wei, Lei and Bons, Joanna and Rose, Jacob and Riley, Rebeccah and Kwok, Ryan and et al.}, year={2024}, month={Mar} } @article{chen_chen_ruszczycky_hilovsky_hostetler_liu_zhou_chang_2024, title={Variation in Biosynthesis and Metal-Binding Properties of Isonitrile-Containing Peptides Produced by Mycobacteria versus Streptomyces}, volume={3}, ISSN={["2155-5435"]}, DOI={10.1021/acscatal.4c00645}, journal={ACS CATALYSIS}, author={Chen, Tzu-Yu and Chen, Jinfeng and Ruszczycky, Mark W. and Hilovsky, Dalton and Hostetler, Tyler and Liu, Xiaojing and Zhou, Jiahai and Chang, Wei-chen}, year={2024}, month={Mar} } @article{phan_manley_skirboll_cha_hilovsky_chang_thompson_liu_makris_2023, title={Excision of a Protein-Derived Amine for p-Aminobenzoate Assembly by the Self-Sacrificial Heterobimetallic Protein CADD}, volume={62}, ISSN={["1520-4995"]}, url={https://doi.org/10.1021/acs.biochem.3c00406}, DOI={10.1021/acs.biochem.3c00406}, abstractNote={Chlamydia protein associating with death domains (CADD), the founding member of a recently discovered class of nonheme dimetal enzymes termed hemeoxygenase-like dimetaloxidases (HDOs), plays an indispensable role in pathogen survival. CADD orchestrates the biosynthesis of p-aminobenzoic acid (pABA) for integration into folate via the self-sacrificial excision of a protein-derived tyrosine (Tyr27) and several additional processing steps, the nature and timing of which have yet to be fully clarified. Nuclear magnetic resonance (NMR) and proteomics approaches reveal the source and probable timing of amine installation by a neighboring lysine (Lys152). Turnover studies using limiting O2 have identified a para-aminobenzaldehyde (pABCHO) metabolic intermediate that is formed on the path to pABA formation. The use of pABCHO and other probe substrates shows that the heterobimetallic Fe/Mn form of the enzyme is capable of oxygen insertion to generate the pABA-carboxylate.}, number={22}, journal={BIOCHEMISTRY}, author={Phan, Han N. and Manley, Olivia M. and Skirboll, Sydney S. and Cha, Lide and Hilovsky, Dalton and Chang, Wei-chen and Thompson, Peter M. and Liu, Xiaojing and Makris, Thomas M.}, year={2023}, month={Nov}, pages={3276–3282} } @article{zhang_bons_scheidemantle_liu_bielska_carrico_rose_heckenbach_scheibye-knudsen_schilling_et al._2023, title={Histone malonylation is regulated by SIRT5 and KAT2A}, volume={26}, ISSN={["2589-0042"]}, DOI={10.1016/j.isci.2023.106193}, abstractNote={The posttranslational modification lysine malonylation is found in many proteins, including histones. However, it remains unclear whether histone malonylation is regulated or functionally relevant. Here, we report that availability of malonyl-co-enzyme A (malonyl-CoA), an endogenous malonyl donor, affects lysine malonylation, and that the deacylase SIRT5 selectively reduces malonylation of histones. To determine if histone malonylation is enzymatically catalyzed, we knocked down each of the 22 lysine acetyltransferases (KATs) to test their malonyltransferase potential. KAT2A knockdown in particular reduced histone malonylation levels. By mass spectrometry, H2B_K5 was highly malonylated and regulated by SIRT5 in mouse brain and liver. Acetyl-CoA carboxylase (ACC), the malonyl-CoA producing enzyme, was partly localized in the nucleolus, and histone malonylation increased nucleolar area and ribosomal RNA expression. Levels of global lysine malonylation and ACC expression were higher in older mouse brains than younger mice. These experiments highlight the role of histone malonylation in ribosomal gene expression.}, number={3}, journal={ISCIENCE}, author={Zhang, Ran and Bons, Joanna and Scheidemantle, Grace and Liu, Xiaojing and Bielska, Olga and Carrico, Chris and Rose, Jacob and Heckenbach, Indra and Scheibye-Knudsen, Morten and Schilling, Birgit and et al.}, year={2023}, month={Mar} } @article{tsai_chuang_li_yu_tzeng_teoh_lindblad_di matteo_cheng_hsueh_et al._2023, title={Immunoediting instructs tumor metabolic reprogramming to support immune evasion}, volume={35}, ISSN={["1932-7420"]}, DOI={10.1016/j.cmet.2022.12.003}, abstractNote={Immunoediting sculpts immunogenicity and thwarts host anti-tumor responses in tumor cells during tumorigenesis; however, it remains unknown whether metabolic programming of tumor cells can be guided by immunosurveillance. Here, we report that T cell-mediated immunosurveillance in early-stage tumorigenesis instructs c-Myc upregulation and metabolic reprogramming in tumor cells. This previously unexplored tumor-immune interaction is controlled by non-canonical interferon gamma (IFNγ)-STAT3 signaling and supports tumor immune evasion. Our findings uncover that immunoediting instructs deregulated bioenergetic programs in tumor cells to empower them to disarm the T cell-mediated immunosurveillance by imposing metabolic tug-of-war between tumor and infiltrating T cells and forming the suppressive tumor microenvironment.}, number={1}, journal={CELL METABOLISM}, author={Tsai, Chin-Hsien and Chuang, Yu-Ming and Li, Xiaoyun and Yu, Yi-Ru and Tzeng, Sheue-Fen and Teoh, Shao Thing and Lindblad, Katherine E. and Di Matteo, Mario and Cheng, Wan-Chen and Hsueh, Pei-Chun and et al.}, year={2023}, month={Jan}, pages={118-+} } @article{liu_duan_liu_wang_2023, title={Metabolomic Analysis of Uterine Luminal Fluid During the Peri-Implantation Period of Pregnancy in Pigs}, volume={101}, ISSN={["1525-3163"]}, DOI={10.1093/jas/skad068.046}, abstractNote={Abstract}, journal={JOURNAL OF ANIMAL SCIENCE}, author={Liu, Bangmin and Duan, Likun and Liu, Xiaojing and Wang, Xiaoqiu}, year={2023}, month={May} } @article{duan_cooper_scheidemantle_locasale_kirsch_liu_2022, title={C-13 tracer analysis suggests extensive recycling of endogenous CO2 in vivo}, volume={10}, ISSN={["2049-3002"]}, DOI={10.1186/s40170-022-00287-8}, abstractNote={Abstract}, number={1}, journal={CANCER & METABOLISM}, author={Duan, Likun and Cooper, Daniel E. and Scheidemantle, Grace and Locasale, Jason W. and Kirsch, David G. and Liu, Xiaojing}, year={2022}, month={Jul} } @article{karampelias_watt_mattsson_ruiz_rezanejad_mi_liu_chu_locasale_korbutt_et al._2022, title={MNK2 deficiency potentiates beta-cell regeneration via translational regulation}, ISSN={["1552-4469"]}, DOI={10.1038/s41589-022-01047-x}, abstractNote={Abstract}, journal={NATURE CHEMICAL BIOLOGY}, author={Karampelias, Christos and Watt, Kathleen and Mattsson, Charlotte L. and Ruiz, Angel Fernandez and Rezanejad, Habib and Mi, Jiarui and Liu, Xiaojing and Chu, Lianhe and Locasale, Jason W. and Korbutt, Gregory S. and et al.}, year={2022}, month={Jun} } @article{duan_scheidemantle_lodge_cummings_pham_wang_kennedy_liu_2022, title={Prioritize biologically relevant ions for data-independent acquisition (BRI-DIA) in LC-MS/MS-based lipidomics analysis}, volume={18}, ISSN={["1573-3890"]}, DOI={10.1007/s11306-022-01913-8}, abstractNote={Data-dependent acquisition (DDA) is the most commonly used MS/MS scan method for lipidomics analysis on orbitrap-based instrument. However, MS instrument associated software decide the top N precursors for fragmentation, resulting in stochasticity of precursor selection and compromised consistency and reproducibility. We introduce a novel workflow using biologically relevant lipids to construct inclusion list for data-independent acquisition (DIA), named as BRI-DIA workflow.To ensure consistent coverage of biologically relevant lipids in LC-MS/MS-based lipidomics analysis.Biologically relevant ion list was constructed based on LIPID MAPS and lipidome atlas in MS-DIAL 4. Lipids were extracted from mouse tissues and used to assess different MS/MS scan workflow (DDA, BRI-DIA, and hybrid mode) on LC-Orbitrap Exploris 480 mass spectrometer.DDA resulted in more MS/MS events, but the total number of unique lipids identified by three methods (DDA, BRI-DIA, and hybrid MS/MS scan mode) is comparable (580 unique lipids across 44 lipid subclasses in mouse liver). Major cardiolipin molecular species were identified by data generated using BRI-DIA and hybrid methods and allowed calculation of cardiolipin compositions, while identification of the most abundant cardiolipin CL72:8 was missing in data generated using DDA method, leading to wrong calculation of cardiolipin composition.The method of using inclusion list comprised of biologically relevant lipids in DIA MS/MS scan is as efficient as traditional DDA method in profiling lipids, but offers better consistency of lipid identification, compared to DDA method. This study was performed using Orbitrap Exploris 480, and we will further evaluate this workflow on other platforms, and if verified by future work, this biologically relevant ion fragmentation workflow could be routinely used in many studies to improve MS/MS identification capacities.}, number={8}, journal={METABOLOMICS}, author={Duan, Likun and Scheidemantle, Grace and Lodge, Mareca and Cummings, Magdalina J. and Pham, Eva and Wang, Xiaoqiu and Kennedy, Arion and Liu, Xiaojing}, year={2022}, month={Jul} } @article{snyder_o'brien_singh_buchan_arroyo_liu_bostwick_varner_angajala_sobol_et al._2021, title={Primary saturation of alpha, beta-unsaturated carbonyl containing fatty acids does not abolish electrophilicity}, volume={350}, ISSN={["1872-7786"]}, DOI={10.1016/j.cbi.2021.109689}, abstractNote={Metabolism of polyunsaturated fatty acids results in the formation of hydroxylated fatty acids that can be further oxidized by dehydrogenases, often resulting in the formation of electrophilic, α,β-unsaturated ketone containing fatty acids. As electrophiles are associated with redox signaling, we sought to investigate the metabolism of the oxo-fatty acid products in relation to their double bond architecture. Using an untargeted liquid chromatography mass spectrometry approach, we identified mono- and di-saturated products of the arachidonic acid-derived 11-oxoeicosatetraenoic acid (11-oxoETE) and mono-saturated metabolites of 15-oxoETE and docosahexaenoic acid-derived 17-oxodocosahexaenoinc acid (17-oxoDHA) in both human A549 lung carcinoma and umbilical vein endothelial cells. Notably, mono-saturated oxo-fatty acids maintained their electrophilicity as determined by nucleophilic conjugation to glutathione while a second saturation of 11-oxoETE resulted in a loss of electrophilicity. These results would suggest that prostaglandin reductase 1 (PTGR1), known only for its reduction of the α,β-unsaturated double bond, was not responsible for the saturation of oxo-fatty acids at alternative double bonds. Surprisingly, knockdown of PTGR1 expression by shRNA confirmed its participation in the formation of 15-oxoETE and 17-oxoDHA mono-saturated metabolites. Furthermore, overexpression of PTGR1 in A549 cells increased the rate and total amount of oxo-fatty acid saturation. These findings will further facilitate the study of electrophilic fatty acid metabolism and signaling in the context of inflammatory diseases and cancer where they have been shown to have anti-inflammatory and anti-proliferative signaling properties.}, journal={CHEMICO-BIOLOGICAL INTERACTIONS}, author={Snyder, Nathaniel W. and O'Brien, James and Singh, Bhupinder and Buchan, Gregory and Arroyo, Alejandro D. and Liu, Xiaojing and Bostwick, Anna and Varner, Erika L. and Angajala, Anusha and Sobol, Robert W. and et al.}, year={2021}, month={Dec} } @article{karampelias_rezanejad_rosko_duan_lu_pazzagli_bertolino_cesta_liu_korbutt_et al._2021, title={Reinforcing one-carbon metabolism via folic acid/Folr1 promotes beta-cell differentiation}, volume={12}, ISSN={["2041-1723"]}, DOI={10.1038/s41467-021-23673-0}, abstractNote={Abstract}, number={1}, journal={NATURE COMMUNICATIONS}, author={Karampelias, Christos and Rezanejad, Habib and Rosko, Mandy and Duan, Likun and Lu, Jing and Pazzagli, Laura and Bertolino, Philippe and Cesta, Carolyn E. and Liu, Xiaojing and Korbutt, Gregory S. and et al.}, year={2021}, month={Jun} } @article{gut_matilainen_meyer_pallijeff_richard_carroll_euro_jackson_isohanni_minassian_et al._2020, title={SUCLA2 mutations cause global protein succinylation contributing to the pathomechanism of a hereditary mitochondrial disease}, volume={11}, ISSN={["2041-1723"]}, DOI={10.1038/s41467-020-19743-4}, abstractNote={Abstract}, number={1}, journal={NATURE COMMUNICATIONS}, author={Gut, Philipp and Matilainen, Sanna and Meyer, Jesse G. and Pallijeff, Pieti and Richard, Joy and Carroll, Christopher J. and Euro, Liliya and Jackson, Christopher B. and Isohanni, Pirjo and Minassian, Berge A. and et al.}, year={2020}, month={Nov} } @article{liu_cooper_cluntun_warmoes_zhao_reid_liu_lund_lopes_garcia_et al._2019, title={Acetate production from glucose and coupling to mitochondrial metabolism in mammals}, volume={79}, ISSN={["1538-7445"]}, DOI={10.1158/1538-7445.SABCS18-792}, abstractNote={Background: In conditions of hyperactive cellular metabolism, excessive cellular nutrient uptake results in incomplete metabolism and excretion of intermediates. These intermediates may serve as unconventional fuel sources satisfy metabolic demands during nutrient scarcity. Interestingly, acetate metabolism provides a parallel pathway for acetyl-CoA production and allows for protein acetylation and lipogenesis independent of citrate conversion to acetyl-CoA. This pathway is important in tumorigenesis, immune alertness, neural plasticity, and other diverse contexts but the origin of acetate has been unclear. Thus, we have conducted a re-evaluation of endogenous acetate generation and the biological relevance. Method: Cancer cells were cultured in RPMI medium with 13 C labelled nutrients in the presence of 18 O 2 . Mouse models of soft tissue sarcoma were generated in a mixed 129/SVJae and C57BL/6 background. A jugular vein catheter was surgically implanted and exteriorized via a vascular access port, which allows infusion of [ 13 C 6 ]-glucose via the venous catheter. Acetate in medium and blood is quantified using [ 2 H 3 ] labelled acetate as the standard after 2-hydrazinoquinoline (HQ) derivatization, and other polar metabolites were directly analyzed after cold methanol extraction. All metabolites were measured using liquid chromatography coupled with high resolution mass spectrometer. Results: By employing multiple-isotope tracing technology, quantitative proteomics, and mouse genetics tools, we demonstrated that acetate is quantitatively generated from pyruvate, the end product of glycolysis and key node in central carbon metabolism in cancer cells and tumor. One reaction mechanism found to generate acetate occur through altered enzyme activity of thiamine-dependent keto acid dehydrogenases, which transforms their activity to keto acid decarboxylases. The other reaction mechanism to generate acetate occur by reaction with reactive oxygen species (ROS), a finding which potentially links this pathway to numerous physiological and pathophysiological processes. Thiamine starvation and the addition of exogeneous ROS greatly stimulated the ROS contribution to acetate production, which can be used to replenish intracellular acetyl groups. Thus, increased acetate production and release could potentially favor the neighboring cells deficient in cytosolic acetyl-CoA, as demonstrated by co-culturing ACLY KO cells with HCT116 cells. Conclusion: We have not only provided direct evidence that acetate arises from endogenous metabolism of glucose in mammalian cells, but also identified the regulatory mechanisms, which involve ROS and mitochondrial functions. Note: This abstract was not presented at the meeting. Citation Format: Xiaojing Liu, Daniel E. Cooper, Ahmad A. Cluntun, Marc O. Warmoes, Steven Zhao, Michael A. Reid, Juan Liu, Peder J. Lund, Mariana Lopes, Benjamin A. Garcia, Kathryn E. Wellen, David G. Kirsch, Jason W. Locasale. Acetate production from glucose and coupling to mitochondrial metabolism in mammals [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 792.}, number={13}, journal={CANCER RESEARCH}, author={Liu, Xiaojing and Cooper, Daniel E. and Cluntun, Ahmad A. and Warmoes, Marc O. and Zhao, Steven and Reid, Michael A. and Liu, Juan and Lund, Peder J. and Lopes, Mariana and Garcia, Benjamin A. and et al.}, year={2019}, month={Jul} } @article{tabilas_wang_liu_locasale_smith_rudd_2019, title={Cutting Edge: Elevated Glycolytic Metabolism Limits the Formation of Memory CD8(+) T Cells in Early Life}, volume={203}, ISSN={["1550-6606"]}, DOI={10.4049/jimmunol.1900426}, abstractNote={Abstract}, number={10}, journal={JOURNAL OF IMMUNOLOGY}, author={Tabilas, Cybelle and Wang, Jocelyn and Liu, Xiaojing and Locasale, Jason W. and Smith, Norah L. and Rudd, Brian D.}, year={2019}, month={Nov}, pages={2571–2576} }