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Acetyl-CoA metabolism in cancer
Open accessAbstract
Few metabolites can claim a more central and versatile role in cell metabolism than acetyl coenzyme A (acetyl-CoA). Acetyl-CoA is produced during nutrient catabolism to fuel the tricarboxylic acid cycle and is the essential building block for fatty acid and isoprenoid biosynthesis. It also functions as a signalling metabolite as the substrate for lysine acetylation reactions, enabling the modulation of protein functions in response to acetyl-CoA availability. Recent years have seen exciting advances in our understanding of acetyl-CoA metabolism in normal physiology and in cancer, buoyed by new mouse models, in vivo stable-isotope tracing approaches and improved methods for measuring acetyl-CoA, including in specific subcellular compartments. Efforts to target acetyl-CoA metabolic enzymes are also advancing, with one therapeutic agent targeting acetyl-CoA synthesis receiving approval from the US Food and Drug Administration. In this Review, we give an overview of the regulation and cancer relevance of major metabolic pathways in which acetyl-CoA participates. We further discuss recent advances in understanding acetyl-CoA metabolism in normal tissues and tumours and the potential for targeting these pathways therapeutically. We conclude with a commentary on emerging nodes of acetyl-CoA metabolism that may impact cancer biology. Acetyl coenzyme A (acetyl-CoA) is a key metabolite in carbohydrate and lipid metabolism and plays a role in signalling through protein acetylation, and the dysregulation of these pathways is a hallmark of various cancers. In this Review, Guertin and Wellen give an overview of acetyl-CoA metabolism in health and in cancer and discuss emerging therapeutic strategies for targeting metabolic pathways involving acetyl-CoA.
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“acetylation relies on acetyl-CoA (Box 1, Figure I); a key node in various metabolic pathways which are commonly dysregulated in cancer [1–3].”
From Acetylation: a new target for protein degradation in cancer (2025) · cites this paper as [1]
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“Protein acetylation is intrinsically linked to metabolism due to its use of key metabolic intermediate acetyl-CoA [1,52].”
From Acetylation: a new target for protein degradation in cancer (2025) · cites this paper as [1]
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Cites
GEPIA: a web server for cancer and normal gene expression profiling and interactive analyses
Tang, Z., Li, C., Kang, B., Gao, G., Li, C., & Zhang, Z. (2017) · Nucleic Acids Research · doi:10.1093/nar/gkx247 · Cited by 9,849
Ferroptosis: mechanisms, biology and role in disease
Jiang, X., Stockwell, B. R., & Conrad, M. (2021) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-020-00324-8 · Cited by 7,973
Ferroptosis: A Regulated Cell Death Nexus Linking Metabolism, Redox Biology, and Disease
Stockwell, B. R., Friedmann Angeli, J. P., Bayir, H., Bush, A. I., Conrad, M., Dixon, S. J., Fulda, S., Gascón, S., Hatzios, S. K., Kagan, V. E., et al. (2017) · Cell · doi:10.1016/j.cell.2017.09.021 · Cited by 7,695
The CoQ oxidoreductase FSP1 acts parallel to GPX4 to inhibit ferroptosis
Bersuker, K., Hendricks, J. M., Li, Z., Magtanong, L., Ford, B., Tang, P. H., Roberts, M. A., Tong, B., Maimone, T. J., Zoncu, R., et al. (2019) · Nature · doi:10.1038/s41586-019-1705-2 · Cited by 3,703
ATP-citrate lyase links cellular metabolism to histone acetylation
Wellen, K. E., Hatzivassiliou, G., Sachdeva, U. M., Bui, T. V., Cross, J. R., & Thompson, C. B. (2009) · Science · doi:10.1126/science.1164097 · Cited by 2,298
Self-citationTargeting Ferroptosis as a Vulnerability in Cancer
Lei, G., Zhuang, L., & Gan, B. (2022) · Nature reviews. Cancer · doi:10.1038/s41568-022-00459-0 · Cited by 2,252
Posttranscriptional Control of T Cell Effector Function by Aerobic Glycolysis
Chang, C.-H., Curtis, J. D., Maggi, L. B., Faubert, B., Villarino, A. V., O’Sullivan, D., Huang, S. C.-C., van der Windt, G. J. W., Blagih, J., Qiu, J., et al. (2013) · Cell · doi:10.1016/j.cell.2013.05.016 · Cited by 2,204
Cellular Fatty Acid Metabolism and Cancer
Currie, E., Schulze, A., Zechner, R., Walther, T. C., & Farese, R. V. (2013) · Cell Metabolism · doi:10.1016/j.cmet.2013.05.017 · Cited by 2,123
DHODH-mediated ferroptosis defence is a targetable vulnerability in cancer
Mao, C., Liu, X., Zhang, Y., Lei, G., Yan, Y., Lee, H., Koppula, P., Wu, S., Zhuang, L., Fang, B., et al. (2021) · Nature · doi:10.1038/s41586-021-03539-7 · Cited by 2,028
Activation of a metabolic gene regulatory network downstream of mTOR complex 1
Düvel, K., Yecies, J. L., Menon, S., Raman, P., Lipovsky, A. I., Souza, A. L., Triantafellow, E., Ma, Q., Gorski, R., Cleaver, S., et al. (2010) · Molecular Cell · doi:10.1016/j.molcel.2010.06.022 · Cited by 2,020
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Metabolic reprogramming, sensing, and cancer therapy
Mao, Y., Xia, Z., Xia, W., & Jiang, P. (2024) · Cell Reports · doi:10.1016/j.celrep.2024.115064 · Cited by 180
The emerging role of protein l-lactylation in metabolic regulation and cell signalling
Ren, H., Tang, Y., & Zhang, D. (2025) · Nature Metabolism · doi:10.1038/s42255-025-01259-0 · Cited by 159
“Acetyl-CoA can then exit the mitochondria as citrate, which is subsequently converted back into acetyl-CoA by ATP citrate lyase to support lipid synthesis and protein acetylation 80 .”
Acetylcarnitine shuttling links mitochondrial metabolism to histone acetylation and lipogenesis
Izzo, L., Trefely, S., Demetriadou, C., Drummond, J. M., Mizukami, T., Kuprasertkul, N., Farria, A. T., Nguyen, P. T., Murali, N., Reich, L. N., et al. (2023) · Science Advances · doi:10.1126/sciadv.adf0115 · Cited by 140
“…exported from mitochondria into acetyl-CoA and oxaloacetate, and acyl-CoA short chain fatty acid synthase 2 (ACSS2), which condenses acetate with coenzyme A. Acetyl-CoA generated by these enzymes is used for de novo lipogenesis (DNL), as well as for acetylation in the nucleus and cytosol ( 1 – 3 ).”
Self-citationMASH: the nexus of metabolism, inflammation, and fibrosis
Steinberg, G. R., Carpentier, A. C., & Wang, D. (2025) · Journal of Clinical Investigation · doi:10.1172/jci186420 · Cited by 135
Epigenetic regulation in cancer
Gu, M., Ren, B., Fang, Y., Ren, J., Liu, X., Wang, X., Zhou, F., Xiao, R., Luo, X., You, L., et al. (2024) · MedComm · doi:10.1002/mco2.495 · Cited by 126
Nutrient-driven histone code determines exhausted CD8 + T cell fates
Ma, S., Dahabieh, M. S., Mann, T. H., Zhao, S., McDonald, B., Song, W., Chung, H., Farsakoglu, Y., Garcia-Rivera, L., Hoffmann, F. A., et al. (2024) · Science · doi:10.1126/science.adj3020 · Cited by 118
Coenzyme A biosynthesis: mechanisms of regulation, function and disease
Barritt, S. A., DuBois-Coyne, S. E., & Dibble, C. C. (2024) · Nature Metabolism · doi:10.1038/s42255-024-01059-y · Cited by 118
“Such acetylation/deacetylation events, mediated by histone acetyl transferases and histone deacetylases, integrate metabolic information (fluctuating free CoA:acetyl-CoA ratios) with other regulatory inputs such as hormone and growth factor signalling 5,12 .”
Emerging mechanisms and promising approaches in pancreatic cancer metabolism
Wu, H., Fu, M., Wu, M., Cao, Z., Zhang, Q., & Liu, Z. (2024) · Cell Death and Disease · doi:10.1038/s41419-024-06930-0 · Cited by 97
“…aggressiveness, and reduced LD abundance can reduce the invasive ability of KRAS-mutant PDAC [80]. β -oxidation of stored lipids can produce acetyl-CoA, which is subsequently shuttled through the TCA cycle, providing a valuable source of ATP and NADPH under conditions of metabolic stress [81].”
BackgroundWan, M., Pan, S., Shan, B., Diao, H., Jin, H., Wang, Z., Wang, W., Han, S., Liu, W., He, J., et al. (2025) · Molecular Cancer · doi:10.1186/s12943-025-02258-1 · Cited by 102
“Acetyl-CoA is generated through the catabolism of glucose, fatty acids, ketone bodies, and proteins [60].”
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Sheng, X., Lin, H., Cole, P. A., & Zhao, Y. (2025) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-025-00876-7 · Cited by 97
“…the role of K ac as a reversible acetate reservoir suggests that some modifications may exist at low global levels mainly because they are metabolically tuned and locally mobilized in response to cellular demands 169–171 , further underscoring that stoichiometry alone does not predict function.”
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He, Y., Song, T., Ning, J., Wang, Z., Yin, Z., Jiang, P., Yuan, Q., Yu, W., & Fan, C. (2024) · Clinical and Translational Medicine · doi:10.1002/ctm2.70070 · Cited by 79
“59 The production process for lactyl-CoA remains less well understood.”
MethodCancer plasticity in therapy resistance: Mechanisms and novel strategies
Niu, X., Liu, W., Yinling, Z., Liu, J., Zhang, J., Li, B., Qiu, Y., Zhao, P., Wang, Z., & Wang, Z. (2024) · Drug Resistance Updates · doi:10.1016/j.drup.2024.101114 · Cited by 68
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Wang, Z., Wang, Y., Li, Z., Xue, W., Hu, S., & Kong, X. (2023) · Frontiers in Pharmacology · doi:10.3389/fphar.2023.1274335 · Cited by 71
“However, acetyl CoA, although present in the mitochondria (Guertin and Wellen, 2023), cannot directly traverse the mitochondrial membrane, necessitating a transport mechanism to enter the cytosol.”
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Biffo, S., Ruggero, D., & Santoro, M. M. (2024) · Cell Metabolism · doi:10.1016/j.cmet.2024.07.022 · Cited by 66
Jiang, Z., Xiong, N., Yan, R., Li, S., Liu, H., Mao, Q., Sun, Y., Shen, S., Ye, L., Gao, P., et al. (2024) · Protein & Cell · doi:10.1093/procel/pwae052 · Cited by 60
“S2C) (Li et al, 2011; Yokomizo et al, 2011), additionally, the levels of acetyl-coA in tumors are high (Guertin and Wellen, 2023), which leads to high basal levels of PDHX K488 acetylation.”
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Hou, Y., Lv, B., Du, J., Ye, M., Jin, H., Yi, Y., & Huang, Y. (2025) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-025-02231-w · Cited by 64
“246 Serum Hcy levels are positively correlated with the progression of liver fi brosis, potentially exerting their effects through the homocysteinylation of the autophagosome/lysosome fusion protein Syntaxin 17 (Stx17).”
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Gautam, J., Wu, J., Lally, J., McNicol, J. D., Fayyazi, R., Ahmadi, E., Oniciu, D. C., Heaton, S., Newton, R. S., Rehal, S., et al. (2025) · Nature · doi:10.1038/s41586-025-09297-0 · Cited by 64
“ATP citrate lyase (ACLY) links substrate availability and mitochondrial metabolism with lipid biosynthesis and gene regulation 5–7 .”
Acetyl-CoA metabolism as a therapeutic target for cancer
Chen, G., Bao, B., Cheng, Y., Tian, M., Song, J., Zheng, L., & Tong, Q. (2023) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2023.115741 · Cited by 54
Metabolic Reprogramming in Cancer: Implications for Immunosuppressive Microenvironment
Aden, D., Sureka, N., Zaheer, S., Chaurasia, J. K., & Zaheer, S. (2024) · Immunology · doi:10.1111/imm.13871 · Cited by 58
“…is exported from the mitochondria to the cytoplasm, where it is cleaved by ATP citrate lyase (ACLY) to produce acetyl-CoA, a building block for FA and cholesterol synthesis [138–140]. α-Ketoglutarate is an essential precursor for amino acid biosynthesis, including glutamate and proline [141].”
The Tricarboxylic Acid Cycle Metabolites for Cancer: Friend or Enemy
Wu, J., Liu, N., Chen, J., Tao, Q., Li, Q., Li, J., Chen, X., & Peng, C. (2024) · Research · doi:10.34133/research.0351 · Cited by 57
“The TCA cycle begins with the entry of acetyl-coenzyme A (CoA) produced by glycolysis, the β -oxidation of fatty acids or the amino acid catabolism [3].”
BackgroundHu, A., Wang, H., Xu, Q., Pan, Y., Jiang, Z., Li, S., Qu, Y., Hu, Y., Wu, H., & Wang, X. (2023) · Redox Biology · doi:10.1016/j.redox.2023.102959 · Cited by 52
“Carnitine palmitoyltransferase 1A (CPT1A) is a mitochondrial enzyme that regulates fatty acid oxidation (FAO), a metabolic pathway that is often upregulated in various cancers and linked to prognosis [5 – 8].”
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Charidemou, E., & Kirmizis, A. (2024) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2024.10.005 · Cited by 49
Wang, R., Zhuang, J., Zhang, Q., Wu, W., Yu, X., Zhang, H., & Xie, Z. (2025) · Experimental Hematology and Oncology · doi:10.1186/s40164-025-00689-6 · Cited by 52
Metabolite regulation of epigenetics in cancer
Wang, P., Chen, L., Xiong, Y., & Ye, D. (2024) · Cell Reports · doi:10.1016/j.celrep.2024.114815 · Cited by 50
Han, X., Wang, D., Liao, Y., Wang, N., Shen, J., Wang, J., Zhang, L., Chen, L., Gao, S., Zong, W., et al. (2024) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2319429121 · Cited by 46
“Pharmacological inhibitors targeting polyamine metabolism have been developed, including difluoromethylornithine (DFMO), a small molecule inhibitor of ODC1, and N1, N11 - diethylnorspermine (DENSpm, also known as BENSpm), a small molecule agonist of SAT1, for cancer treat ment (9, 11–13).”
MethodSOAT1 regulates cholesterol metabolism to induce EMT in hepatocellular carcinoma
Fu, R., Xue, W., Liang, J., Li, X., Zheng, J., Wang, L., Zhang, M., & Meng, J. (2024) · Cell Death and Disease · doi:10.1038/s41419-024-06711-9 · Cited by 42
“3-hydroxy-3-methylglutaryl CoA synthase (HMGCS) can convert acetyl coenzyme A into HMG-CoA, which plays an important role in the process of cholesterol synthesis [16].”
Pan, J.-J., Xie, S., Zheng, X. M., Xu, J., Xu, H. Y., Yin, R.-Q., Luo, Y., Li, S., Chen, Z.-R., Chen, Y.-R., et al. (2024) · Cancer Letters · doi:10.1016/j.canlet.2024.216903 · Cited by 42
Wang, Y., Su, K., Wang, C., Deng, T., Liu, X., Sun, S., Jiang, Y., Zhang, C., Xing, B., & Du, X. (2024) · Cell Death and Disease · doi:10.1038/s41419-024-06951-9 · Cited by 42
“The majority of acetyl-CoA is generated in the mitochondrial matrix, and powers the tricarboxylic acid (TCA) cycle and electron transport chain [18, 19].”
BackgroundSubcellular one carbon metabolism in cancer, aging and epigenetics
Bernasocchi, T., & Mostoslavsky, R. (2024) · Frontiers in Epigenetics and Epigenomics · doi:10.3389/freae.2024.1451971 · Cited by 44
“…(SAM) is the universal donor for methylation reactions, and adenosine triphosphate (ATP) is a fundamental component for phosphorylation (Wei et al., 1999; Rossetto et al., 2012; Etchegaray and Mostoslavsky, 2016; Mentch and Locasale, 2016; Boon et al., 2020; Guertin and Wellen, 2023).”
BackgroundVerma, A., & Lindroth, A. M. (2025) · Experimental & Molecular Medicine · doi:10.1038/s12276-025-01537-7 · Cited by 47
“In various cancers, elevated ACLY expression is linked to increased histone acetylation, driving oncogenes such as MYC and HIF-1 α , which play pivotal roles in tumor progression 24 .”
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Zhang, Y., Shen, X. L., Shen, Y., Wang, C., Yu, C., Han, J., Cao, S., Qian, L., Ma, M., Huang, S., et al. (2025) · Nature · doi:10.1038/s41586-025-09745-x · Cited by 48
Wang, X., Li, Y., Hou, X., Li, J., & Ma, X. (2024) · Cell Communication and Signaling · doi:10.1186/s12964-024-01792-7 · Cited by 38
“Acetyl-CoA is at the core of cancer metabolism, which plays a critical role in FA and cholesterol synthesis, and histone acetylation, thus affecting the proliferative and invasive ability of cancer cell [52].”
BackgroundHuang, L., Xu, R. F., Chen, S., Lin, C., Li, W., Li, S., Saw, P. E., Zhang, L., & Xu, X. (2025) · Molecular Cancer · doi:10.1186/s12943-025-02274-1 · Cited by 41
“As a classic enzyme, ACSL3 can catalyze free long-chain fatty acids into fatty acyl-CoA esters that can be converted into various lipids and their derivatives, such as lysophosphatidic acid (LPA), phosphatidic acid (PA), diacylglycerol (DAG), and triacylglyc-eride (TAG) [24, 38, 39].”
Li, Y., Jiang, H., Jia, Y., Liao, Y., Shao, C., Zhou, Y., Li, J., Liao, Y., Huang, H., Pan, Y., et al. (2024) · Advanced Science · doi:10.1002/advs.202308422 · Cited by 37
Jiang, Y., Wang, H., Li, B., Liu, J., Zhang, X., Wang, Y., Peng, J., Gao, L., Wang, X., Hu, S., et al. (2024) · Metabolism · doi:10.1016/j.metabol.2024.156041 · Cited by 39
Korobkina, E. D., Calejman, C. M., Haley, J. D., Kelly, M. E., Li, H., Gaughan, M., Chen, Q., Pepper, H. L., Ahmad, H., Boucher, A., et al. (2024) · Nature Metabolism · doi:10.1038/s42255-024-01143-3 · Cited by 34
“…source of cytosolic acetyl-CoA for de novo lipogenesis (DNL), the process of synthesizing lipids from non-lipid precursors such as glucose, while acyl-CoA synthetase short chain family member 2 (ACSS2) can provide an alternative source of acetyl-CoA from acetate under certain conditions 17,18 .”
Self-citationYates, J., Kraft, A., & Boeva, V. (2025) · Genome biology · doi:10.1186/s13059-025-03559-w · Cited by 35
“…found that four consistently upregulated pathways in the studied cancer types were the glycerol phosphate shuttle (7/7 studies), biotin-utilizing proteins (7/7 studies), coenzyme A (CoA) metabolism (5/7 studies), and xenobiotic metabolism (5/7 studies), all with established roles in cancer [51–56].”
Extracellular vesicles in metabolic perspective: mechanism and targeted therapy
Sheng, Q., Wu, Z., Li, W., Wang, L., Xu, H., Wang, W., Yan, Z., Ge, G., Xu, Y., & Geng, D. (2025) · Journal of Nanobiotechnology · doi:10.1186/s12951-025-03763-7 · Cited by 36
“Subsequently, acetyl-CoA is metabolized by the TCA cycle to produce metabolites such as NADH and FADH2 [75].”
Gilglioni, E. H., Li, A., St‐Pierre‐Wijckmans, W., Shen, T.-K., Pérez-Chávez, I., Hovhannisyan, G., Lisjak, M., Negueruela, J., Vandenbempt, V., Bauzá‐Martinez, J., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-53733-0 · Cited by 33
“Monitoring the percentages of alpha helix, beta sheet, loops, and coil during the 200 ns molecular dynamics simulation indicated that there were no significant changes in either the phosphorylated or non-phosphorylated protein, nor any differences between the two proteins.”
Li, W., Han, J., Huang, B., Xu, T., Wan, Y., Luo, D., Kong, W., Yu, Y. H., Zhang, L., Nian, Y., et al. (2025) · The EMBO Journal · doi:10.1038/s44318-025-00369-5 · Cited by 39
“In addition to SLC25A1-ACLY axis, which regulates intracellular levels of acetyl-CoA, ACSS1/2 and pyruvate dehydrogenase complex (PDC) also can use acetate or pyruvate to generate acetyl-CoA (Guertin and Wellen, 2023).”
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Wang, H., Yi, X., Wang, X., Yang, Y., Zhang, H., Wang, H., Chen, J., Zhang, B., Guo, S., Wu, L., et al. (2024) · Cell Reports · doi:10.1016/j.celrep.2024.115015 · Cited by 31
Luo, H.-Y., Fang, J., Zhang, W.-H., Chan, K.-C., Chan, Y.-M., Dong, C.-X., Li, S., Lü, A., & Xu, J. (2024) · Journal of Advanced Research · doi:10.1016/j.jare.2024.12.002 · Cited by 34
“It serves as a pivotal building block, not only participating in the synthesis of fatty acids and isoprenoids but also fueling the tricarboxylic acid cycle [55].”
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Wang, C., & Ma, X. (2025) · Clinical and Translational Medicine · doi:10.1002/ctm2.70145 · Cited by 32
Li, L., Tang, Q., Ge, J., Wang, D., Mo, Y., Zhang, Y., Wang, Y., Xiong, F., Yan, Q., Liao, Q., et al. (2024) · Clinical and Translational Medicine · doi:10.1002/ctm2.1766 · Cited by 30
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Sahoo, S. S., & Manna, D. (2025) · Small · doi:10.1002/smll.202412462 · Cited by 28
Hu, S., Heng, H., Yang, F., Wang, M., Liu, G., Xiang, Y., & Miao, H. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1735873 · Cited by 32
“The TCA cycle begins with acetyl-CoA, derived from glycolysis, fatty acid b -oxidation, or amino acid catabolism (44).”
Advances in regulation and function of stearoyl-CoA desaturase 1 in cancer, from bench to bed
Guo, Z., Huo, X., Li, X., Jiang, C., & Xue, L. (2023) · Science China Life Sciences · doi:10.1007/s11427-023-2352-9 · Cited by 28
“Lita et al. (2021) found that IDH1 mutation and D-2-HG caused the upregulation of SCD1 and SCD5, resulting in increased MUFAs and their phospholipids in ER.”
BackgroundInfluentialLiu, R., Wang, C., Tao, Z., & Hu, G. (2025) · Biomedicines · doi:10.3390/biomedicines13081895 · Cited by 28
“Consequently, cancer cells cunningly utilize acetyl-CoA-associated metabolism to reprogram lipid metabolism, aggravating the tumorigenesis [65].”
Jia, X., Zhang, Q., Chen, M., Wang, Y., Lin, S., Pan, Y., Cheng, P., Li, M., Zhang, Y., Ye, J., et al. (2023) · Frontiers in Plant Science · doi:10.3389/fpls.2023.1235687 · Cited by 26
Zhao, Y., Guo, M., Pei, T., Shang, C., Chen, Y., Zhao, L., Lu, Y., Liang, C., Wang, J., & Zhang, J. (2025) · Advanced Science · doi:10.1002/advs.202413255 · Cited by 24
Yang, L. C., You, J., Yang, X., Jiao, R., Xu, J., Zhang, Y., Mi, W., Zhu, L., Ye, Y., Ren, R., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-57334-3 · Cited by 28
“Acetyl-CoA, the lipogenic precursor and acetylation substrate, plays compartment-speci fi c roles in physiological and pathological processes, including cellular senescence 35 .”
Shi, Y., Tang, Q., Sheng, S., Jiang, H., Jin, C., Zhou, C., Xie, C., Zheng, L., Zhang, D., Xu, H., et al. (2025) · Advanced Science · doi:10.1002/advs.202414902 · Cited by 24
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Li, W., Yu, C., Zhang, X., Gu, Y., He, X., Xu, R., Xu, J. F., Yu, G., & Wu, Y. (2025) · Molecular Biomedicine · doi:10.1186/s43556-025-00300-8 · Cited by 28
“Although cellular acetyl-CoA exhibits compartmentalized distribution [7], elevated FAS and glucose deprivation in TADCs may deplete nuclear acetyl-CoA pools, disrupting expression of MHC-like genes.”
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Lv, M., Yang, X., Xu, C., Song, Q., Zhao, H., Sun, T., Liu, J., Zhang, Y., Sun, G., Xue, Y., et al. (2025) · Advanced Science · doi:10.1002/advs.202412553 · Cited by 29
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Liao, L., Xu, H., Zhao, Y., & Zheng, X. (2023) · Frontiers of Medicine · doi:10.1007/s11684-023-1025-7 · Cited by 22
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“In addition to the oxidative decarboxylation of glycolytic pyruvate in mitochondria, acetyl-CoA can be obtained by β-oxidation of FAs, catabolism of branched-chain amino acids (leucine and isoleucine) and oxidative decomposition of ketone bodies [204, 205].”
Acetylation: a new target for protein degradation in cancer
Crawford, C. E. W., & Burslem, G. M. (2025) · Trends in Cancer · doi:10.1016/j.trecan.2025.01.013 · Cited by 20
Metabolic reprogramming of tumor microenviroment by engineered bacteria
Wang, H., Xu, F., & Wang, C. (2025) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2025.03.003 · Cited by 20
Nutrient allocation fuels T cell-mediated immunity
Longo, J., Watson, M. J., Williams, K. S., Sheldon, R. D., & Jones, R. G. (2025) · Cell Metabolism · doi:10.1016/j.cmet.2025.09.008 · Cited by 19
Barnett, K. R., Mobley, R. J., Diedrich, J. D., Bergeron, B. P., Bhattarai, K. R., Monovich, A. C., Narina, S., Yang, W., Crews, K. R., Manring, C. S., et al. (2023) · Cell Genomics · doi:10.1016/j.xgen.2023.100442 · Cited by 22
Targeting mitochondrial metabolism with CPI-613 in chemoresistant ovarian tumors
Udumula, M. P., Rashid, F., Singh, H., Pardee, T., Luther, S., Bhardwaj, T., Anjaly, K., Piloni, S., Hijaz, M., Gogoi, R. P., et al. (2024) · Journal of Ovarian Research · doi:10.1186/s13048-024-01546-6 · Cited by 20
Nuclear Acly protects the liver from ischemia-reperfusion injury
Gao, W., Zhang, L., Li, Z., Wu, T., Lang, C., Mulholland, M. W., & Zhang, W. (2023) · Hepatology · doi:10.1097/hep.0000000000000692 · Cited by 19
“[5,6] Due to the impermeability of the mitochondrial membrane, cellular AcCoA is compartmentalized into 2 distinct pools: nucleocytosolic and mitochondrial pools.”
Unraveling the metabolic‒epigenetic nexus: a new frontier in cardiovascular disease treatment
Ouyang, J., Wu, D.-D., Gan, Y., Tang, Y., Wang, H., & Huang, J. (2025) · Cell Death and Disease · doi:10.1038/s41419-025-07525-z · Cited by 21
Fructose and glucose from sugary drinks enhance colorectal cancer metastasis via SORD
Feng, T., Luo, Q., Liu, Y., Jin, Z., Skwarchuk, D., Lee, R., Nam, M., Asara, J. M., Adye, D. R., Lorenzi, P. L., et al. (2025) · Nature Metabolism · doi:10.1038/s42255-025-01368-w · Cited by 22
“8b) 30–32 .”
Randhawa, J., & Pålsson‐McDermott, E. M. (2025) · Journal of Inflammation · doi:10.1186/s12950-025-00461-x · Cited by 21
“Like many other metabolites, acetyl-CoA diffuse to the nucleus passively through the nuclear pores; or is generated in the nucleus from pyruvate citrate or acetate by nuclear PDH, ATP citrate lyase (ACLY) or acyl-CoA synthetase short-chain family member 2 (ACSS2), respectively [18, 20].”
Bang, S., Choi, S.-H., & Jeong, S. M. (2025) · Cells · doi:10.3390/cells14241956 · Cited by 22
Lactate metabolism and lactylation in cancer: from pathogenesis to therapeutic advances
Fang, C., Zhou, S., Yu, K., Zhang, L., Lian, W., Tie, X., Chen, S., Dai, J., Li, Q. H., & Wang, X. (2026) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-026-02672-x · Cited by 28
“115,419 Under aerobic conditions, pyruvate is predominantly converted into acetyl-CoA in the mitochondria and further metabolized via the TCA cycle.”
A genetically encoded fluorescent biosensor for visualization of acetyl-CoA in live cells
Smith, J. J., Valentino, T. R., Ablicki, A. H., Banerjee, R., Colligan, A. R., Eckert, D. M., Desjardins, G. A., & Diehl, K. L. (2025) · Cell chemical biology · doi:10.1016/j.chembiol.2025.01.002 · Cited by 19
Research progresses on mitochondrial-targeted biomaterials for bone defect repair
Wang, S., Liu, J., Zhou, L., Xu, H., Zhang, D., Zhang, X., Wang, Q., & Zhou, Q. H. (2024) · Regenerative Biomaterials · doi:10.1093/rb/rbae082 · Cited by 18
Lai, Y., Wang, S., Ren, T., Shi, J. J., Qian, Y., Wang, S., Zhou, M., Watanabe, R., Li, M., Ruan, X., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-59786-z · Cited by 23
“Membranes were incubated with antibodies against H3K9ac, H3K27ac, p-PI3K (p85 (Tyr458)/p55 (Tyr199), p-AKT (Ser473), p-S6 (S235/236), p-mTOR (Ser2448), mTOR, Raptor, TIGIT, IKK α , IKK β , p-I κ B α (Ser32), I κ B α , p-p65 (Ser536), p65, ZAP70, p-ZAP70, LCK, p-LCK, β -actin, ACSS1, ACSS2, ACLY, p-CD226, and histone H…”
InfluentialChe, Z., Xue, W., Zhao, X., Hu, C., & Tian, Y. (2025) · Clinical and Translational Gastroenterology · doi:10.14309/ctg.0000000000000914 · Cited by 20
“This may support tumor cell growth and survival under unfavorable conditions (71,72).”
Zhang, M., Cai, F., Guo, J., Liu, S., Ma, G., Cai, M., Zhang, R., & Deng, J. (2024) · Cell Death and Disease · doi:10.1038/s41419-024-06666-x · Cited by 18
ALDH1A3-acetaldehyde metabolism potentiates transcriptional heterogeneity in melanoma
Lu, Y., Trávníčková, J., Badonyi, M., Rambow, F., Coates, A., Khan, Z., Júnior, J. G. M., Murphy, L. C., Garcia-Martinez, P., Marais, R., et al. (2024) · Cell Reports · doi:10.1016/j.celrep.2024.114406 · Cited by 20
Protein lipoylation in cancer: metabolic reprogramming and therapeutic potential
Li, S., Liu, Y., Hu, W., Deng, A., Ren, X., Chen, L., Lu, Y., Wu, Y., Huang, H., Cao, J., et al. (2025) · Cell Death Discovery · doi:10.1038/s41420-025-02718-z · Cited by 17
“Acetyl-CoA is not only a TCA cycle fuel, but also a key precursor for de novo synthesis of fatty acids [54].”
Mitochondrial targets in hyperammonemia: Addressing urea cycle function to improve drug therapies
Moedas, M. F., Simões, R. J., & Silva, M. F. B. (2024) · Biochemical Pharmacology · doi:10.1016/j.bcp.2024.116034 · Cited by 18
The Metabolism of Coenzyme A and Its Derivatives Plays a Crucial Role in Diseases
Xie, J., Chen, X., Zheng, M., Zhu, J., & Mao, H. (2024) · Frontiers in Bioscience-Landmark · doi:10.31083/j.fbl2904143 · Cited by 18
Macropinocytosis at the crossroad between nutrient scavenging and metabolism in cancer
Rainero, E. (2024) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2024.102359 · Cited by 17
A novel insight into cancer therapy: Lipid metabolism in tumor-associated macrophages
Ren, Y., Wang, M., Yuan, H., Wang, Z., & Yu, L. (2024) · International Immunopharmacology · doi:10.1016/j.intimp.2024.112319 · Cited by 17
Phospholipid Biosynthesis: An Unforeseen Modulator of Nuclear Metabolism
Qiu, H., & Ye, C. (2025) · Biology of the Cell · doi:10.1111/boc.70002 · Cited by 18
Systemic proteome phenotypes reveal defective metabolic flexibility in Mecp2 mutants
Zlatic, S. A., Werner, E., Surapaneni, V., Lee, C. E., Gokhale, A., Singleton, K. S., Duong, D. M., Crocker, A. J., Gentile, K. L., Middleton, F. A., et al. (2023) · Human Molecular Genetics · doi:10.1093/hmg/ddad154 · Cited by 15
Comparative Analysis of Drug-like EP300/CREBBP Acetyltransferase Inhibitors
Crawford, M. C., Tripu, D. R., Barritt, S. A., Jing, Y., Gallimore, D., Kales, S. C., Bhanu, N. V., Xiong, Y., Fang, Y., Butler, K. A. T., et al. (2023) · ACS Chemical Biology · doi:10.1021/acschembio.3c00293 · Cited by 15
Huang, X., Chen, X., Wan, G., Yang, D., Zhu, D., Jia, L., & Zheng, J. (2024) · BMC Cancer · doi:10.1186/s12885-024-11982-8 · Cited by 15
“A lack of pantothenic acid and coenzyme A can lead to DNA loss and mutation, thereby increasing the risk of developing tumors [36].”
BackgroundLi, R., Li, Y., Song, Z., Gu, Y., Jiao, X., Wan, C., Liu, T., Zhang, R., Gao, R., & Wang, X. (2024) · International Journal of Nanomedicine · doi:10.2147/ijn.s478308 · Cited by 15
“15 Therefore, inhibiting ACLY may downregulate acetyl-CoA levels in tumor cells, leading to decreased fatty acid and cholesterol production.”
BackgroundRashad, S., & Marahleh, A. (2025) · Wiley Interdisciplinary Reviews - RNA · doi:10.1002/wrna.70011 · Cited by 14
“…cell cycle, immunity, and development (Achour and Oberdoerffer 2024; Broly et al. 2022), conditions in which acetyl Co-A itself plays an important role (Guertin and Wellen 2023; Lee et al. 2014; Moussaieff et al. 2015), which signifies the intimate links be-tween ac 4 C and acetyl Co-A metabolism.”
Derepressing nuclear pyruvate dehydrogenase induces therapeutic cancer cell reprogramming
Zhao, T., He, L., Wong, L. P., Mei, S., Xia, J., Xu, Y., Vranken, J. G. V., Mazzola, M. C., Chen, L., Rhee, C., et al. (2025) · Cell Metabolism · doi:10.1016/j.cmet.2025.05.009 · Cited by 14
Sun, Y.-H., Zhang, J.-X., Jin, H.-S., & Huang, J. (2025) · Current Issues in Molecular Biology · doi:10.3390/cimb47090751 · Cited by 13
“Cellular acetyl-CoA levels are regulated by nutritional status: feeding states promote glycolysis and fatty acid oxidation to generate abundant acetyl-CoA [87], while fasting states reduce it.”
Sung, Y., Kim, D. K., Kim, J. S., Kim, S.-J., Kim, J. H., & Han, J. M. (2026) · Experimental & Molecular Medicine · doi:10.1038/s12276-026-01697-0 · Cited by 18
“A central feature of this adaptation is the strategic utilization of acetyl-CoA, a pivotal hub linking glucose and lipid metabolism, to drive lipid synthesis and remodeling 122,124 .”
Ali, M. K., Liu, X., Li, J., Zhu, X., Sen, B., & Wang, G. (2023) · Antioxidants · doi:10.3390/antiox12051034 · Cited by 14
“The formation of acetyl CoA is a crucial step that fuels the TCA cycle and provides the necessary building units for the biosynthesis of fatty acids and isoprenoids [52,53].”
BackgroundTodisco, S., Iacobazzi, D., Santarsiero, A., Convertini, P., & Infantino, V. (2025) · Molecular Metabolism · doi:10.1016/j.molmet.2025.102233 · Cited by 15
“Acetyl CoA acts as a donor for the acetylation of histones by lysine acetyltransferases (KATs) [80].”
Szabó, E., Nagy, B., Czajlik, A., Komlódi, T., Ozohanics, O., Tretter, L., & Ambrus, A. (2024) · Sub-cellular biochemistry/Subcellular biochemistry · doi:10.1007/978-3-031-58843-3_13 · Cited by 14
Anti‐Tumor Strategies Targeting Nutritional Deprivation: Challenges and Opportunities
Shi, J., Han, W., Wang, J., & Kong, X. (2025) · Advanced Materials · doi:10.1002/adma.202415550 · Cited by 14
Liu, G., Zhang, H., Chen, S., Gao, J., Zhao, H., Dong, Y., Liu, C., Wei, X., Li, T., Lu, C., et al. (2025) · Cancer Research · doi:10.1158/0008-5472.can-25-0419 · Cited by 13
Zhang, Q., Jia, X., Chen, M.-H., Wang, Y.-H., Lin, S., Pan, Y., Cheng, P., Li, M., Zhang, Y., Luo, Z., et al. (2023) · LWT · doi:10.1016/j.lwt.2023.115462 · Cited by 12
Chronic hypoxia stabilizes 3βHSD1 via autophagy suppression
Qin, L., Berk, M. P., Chung, Y., Cui, D., Zhu, Z., Chakraborty, A. A., & Sharifi, N. (2024) · Cell Reports · doi:10.1016/j.celrep.2023.113575 · Cited by 12
“49 The expression of both ACSS1 and ACSS2 was decreased in HR cells under chronic hypoxia (Figures S11A and S11B).”
Background
Metadata
- Authors
- Guertin, D. A., & Wellen, K. E.
- Affiliations
- University of Massachusetts Chan Medical School (US)
- University of Pennsylvania (US)
- Corresponding author
- Guertin, David A.
- Wellen, Kathryn E.
- Venue
- Nature Reviews Cancer
- Published
- 2023-01-19
- Volume
- 23
- Issue
- 3
- Pages
- 156-172
- ISSN
- 1474-175X (ISSN-L)
- 1474-1768
- PMC
- PMC11137663
- OpenAlex
- W4317436153
- Cited by
- 303
- References
- 200
- Citations by year
- 2026: 85 · 2025: 120 · 2024: 69 · 2023: 29
- FWCI
- 9.57
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Nature reviews. Cancer (publishedVersion, cc-by)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion, cc-by)
- Funders
- National Institutes of Health
- National Cancer Institute (R01CA174761, R01CA248315, R01CA228339, R01CA262055)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK094004, R01DK116005, R01DK127175)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Lipids, and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Keywords
- acetyl-CoA metabolism, cancer metabolism, TCA cycle, fatty acid synthesis, isoprenoid biosynthesis, lysine acetylation, protein acetylation, metabolic signalling, stable isotope tracing
- MeSH terms
- Acetyl Coenzyme A, Animals, Disease Models, Animal, Humans, Neoplasms, Mice, Metabolic Networks and Pathways
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