Acetyl-CoA metabolism in cancer

Guertin, David A.; Wellen, Kathryn E.

doi:10.1038/s41568-022-00543-5

Cited by 303Cancer, Lipids, and MetabolismCancer, Hypoxia, and MetabolismMetabolism, Diabetes, and Cancer

Acetyl-CoA metabolism in cancer

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Guertin, David A., Wellen, Kathryn E.·2023·Nature Reviews Cancer

DOI 10.1038/s41568-022-00543-5PMC PMC11137663

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Abstract

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 depends on acetyl-CoA, a central metabolite in pathways frequently dysregulated in cancer.
“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]
Protein acetylation is intrinsically linked to metabolism due to its use of acetyl-CoA.
“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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Kim, C.-W., Addy, C., Kusunoki, J., Anderson, N. N., Deja, S., Fu, X., Burgess, S. C., Cai, L., Ruddy, M., Chakravarthy, M. V., et al. (2017) · Cell Metabolism · doi:10.1016/j.cmet.2017.08.011 · Cited by 105 · see citing works
Targeting ACSS2 with a Transition-State Mimetic Inhibits Triple-Negative Breast Cancer Growth
Miller, K. D., Pniewski, K. A., Perry, C. E., Papp, S. B., Shaffer, J. D., Velasco‐Silva, J. N., Casciano, J. C., Aramburu, T. M., Srikanth, Y. V. V., Cassel, J. A., et al. (2021) · Cancer Research · doi:10.1158/0008-5472.can-20-1847 · Cited by 101 · see citing works
Adipocyte mesenchymal transition contributes to mammary tumor progression
Zhu, Q., Zhu, Y., Hepler, C., Zhang, Q., Park, J., Gliniak, C. M., Henry, G. H., Crewe, C., Bu, D., Zhang, Z., et al. (2022) · Cell Reports · doi:10.1016/j.celrep.2022.111362 · Cited by 99 · see citing works
An actionable sterol-regulated feedback loop modulates statin sensitivity in prostate cancer
Longo, J., Mullen, P., Yu, R., van Leeuwen, J. E., Masoomian, M., Woon, D. T. S., Wang, Y. Z., Chen, E. X., Hamilton, R. J., Sweet, J., et al. (2019) · Molecular Metabolism · doi:10.1016/j.molmet.2019.04.003 · Cited by 98 · see citing works
ATP-citrate lyase: genetics, molecular biology and therapeutic target for dyslipidemia
Burke, A. C., & Huff, M. W. (2017) · Current Opinion in Lipidology · doi:10.1097/mol.0000000000000390 · Cited by 91 · see citing works
Incorporation of radioactive citrate into fatty acids
Srere, P. A., & Bhaduri, A. (1962) · Biochimica et Biophysica Acta · doi:10.1016/0006-3002(62)90205-6 · Cited by 87 · cited 1× · see citing works
“Specific cancer genetic alterations have been shown to promote mevalonate pathway dependence, including TP53 loss in HCC, TP53 mutation in breast cancer and t(4;14) chromosomal translocation in multiple myeloma.”
Background
Inhibition of hepatic lipogenesis enhances liver tumorigenesis by increasing antioxidant defence and promoting cell survival
Nelson, M. E., Lahiri, S., Chow, J. D. Y., Byrne, F., Hargett, S., Breen, D. S., Olzomer, E. M., Wu, L. E., Cooney, G., Turner, N., et al. (2017) · Nature Communications · doi:10.1038/ncomms14689 · Cited by 86 · see citing works
The incorporation of citrate carbon into fatty acids
Bhaduri, A., & Srere, P. A. (1963) · Biochimica et Biophysica Acta · doi:10.1016/0006-3002(63)90747-9 · Cited by 85 · see citing works
Targeting ACLY sensitizes castration-resistant prostate cancer cells to AR antagonism by impinging on an ACLY-AMPK-AR feedback mechanism
Shah, S., Carriveau, W. J., Li, J., Campbell, S. L., Kopinski, P. K., Lim, H., Daurio, N. A., Trefely, S., Won, K., Wallace, D. C., et al. (2016) · Oncotarget · doi:10.18632/oncotarget.9666 · Cited by 83 · see citing works
Self-citation
Nature and Nurture: What Determines Tumor Metabolic Phenotypes?
Mayers, J. R., & Heiden, M. G. V. (2017) · Cancer Research · doi:10.1158/0008-5472.can-17-0165 · Cited by 83 · see citing works
Fat Induces Glucose Metabolism in Nontransformed Liver Cells and Promotes Liver Tumorigenesis
Broadfield, L. A., Duarte, J. A. G., Schmieder, R., Broekaert, D., Veys, K., Planque, M., Vriens, K., Karasawa, Y., Napolitano, F., Fujita, S., et al. (2021) · Cancer Research · doi:10.1158/0008-5472.can-20-1954 · Cited by 83 · see citing works
ACSS2-mediated acetyl-CoA synthesis from acetate is necessary for human cytomegalovirus infection
Vysochan, A., Sengupta, A., Weljie, A. M., Alwine, J. C., & Yu, Y. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1614268114 · Cited by 78 · see citing works
Adipocyte ACLY Facilitates Dietary Carbohydrate Handling to Maintain Metabolic Homeostasis in Females
Fernandez, S., Viola, J. M., Torres, A., Wallace, M., Trefely, S., Zhao, S., Affronti, H. C., Gengatharan, J. M., Guertin, D. A., Snyder, N. W., et al. (2019) · Cell Reports · doi:10.1016/j.celrep.2019.04.112 · Cited by 77 · see citing works
Self-citation
Purification and Physicochemical Properties of ATP Citrate (pro‐3S) Lyase from Lactating Rat Mammary Gland and Studies of Its Reversible Phosphorylation
Guy, P. S., Cohen, P., & Hardie, D. G. (1981) · European Journal of Biochemistry · doi:10.1111/j.1432-1033.1981.tb05160.x · Cited by 73 · see citing works
MFN2-driven mitochondria-to-nucleus tethering allows a non-canonical nuclear entry pathway of the mitochondrial pyruvate dehydrogenase complex
Zervopoulos, S. D., Boukouris, A. E., Saleme, B., Haromy, A., Tejay, S., Sutendra, G., & Michelakis, E. D. (2022) · Molecular Cell · doi:10.1016/j.molcel.2022.02.003 · Cited by 72 · see citing works
IGF1-mediated HOXA13 overexpression promotes colorectal cancer metastasis through upregulating ACLY and IGF1R
Qiao, C., Huang, W., Chen, J., Feng, W., Zhang, T., Wang, Y., Liu, D., Ji, X., Xie, M., Sun, M., et al. (2021) · Cell Death and Disease · doi:10.1038/s41419-021-03833-2 · Cited by 69 · see citing works
Enzymatic transfer of acetate on histones from lysine reservoir sites to lysine activating sites
Mendoza, M. R., Egervári, G., Sidoli, S., Donahue, G., Alexander, D. C., Sen, P., Garcia, B. A., & Berger, S. L. (2022) · Science Advances · doi:10.1126/sciadv.abj5688 · Cited by 67 · see citing works
In vivo isotope tracing reveals the versatility of glucose as a brown adipose tissue substrate
Jung, S. M., Doxsey, W. G., Le, J., Haley, J. D., Mazuecos, L., Luciano, A. K., Li, H., Jang, C., & Guertin, D. A. (2021) · Cell Reports · doi:10.1016/j.celrep.2021.109459 · Cited by 62 · see citing works
Self-citation
Targeting ACLY Attenuates Tumor Growth and Acquired Cisplatin Resistance in Ovarian Cancer by Inhibiting the PI3K–AKT Pathway and Activating the AMPK–ROS Pathway
Wei, X., Shi, J., Lin, Q., Ma, X., Pang, Y., Mao, H., Li, R., Lü, W., Wang, Y., & Liu, P. (2021) · Frontiers in Oncology · doi:10.3389/fonc.2021.642229 · Cited by 61 · see citing works
The Bidirectional Relationship Between Cancer Epigenetics and Metabolism
Izzo, L., Affronti, H. C., & Wellen, K. E. (2020) · Annual Review of Cancer Biology · doi:10.1146/annurev-cancerbio-070820-035832 · Cited by 60 · see citing works
Self-citation
NaCT/SLC13A5 facilitates citrate import and metabolism under nutrient-limited conditions
Kumar, A., Cordes, T., Thalacker‐Mercer, A. E., Pajor, A. M., Murphy, A. N., & Metallo, C. M. (2021) · Cell Reports · doi:10.1016/j.celrep.2021.109701 · Cited by 60 · see citing works
O-GlcNAc transferase regulates glioblastoma acetate metabolism via regulation of CDK5-dependent ACSS2 phosphorylation
Ciraku, L., Bacigalupa, Z. A., Ju, J., Moeller, R. A., Minh, G. L., Lee, R. H., Smith, M. D., Ferrer, C. M., Trefely, S., Izzo, L., et al. (2022) · Oncogene · doi:10.1038/s41388-022-02237-6 · Cited by 58 · see citing works
Self-citation
Molecular basis for acetyl-CoA production by ATP-citrate lyase
Wei, X., Schultz, K. C., Bazilevsky, G. A., Vogt, A. D., & Marmorstein, R. (2019) · Nature Structural & Molecular Biology · doi:10.1038/s41594-019-0351-6 · Cited by 58 · see citing works
Acetyl-CoA flux regulates the proteome and acetyl-proteome to maintain intracellular metabolic crosstalk
Dieterich, I. A., Lawton, A. J., Peng, Y., Yu, Q., Rhoads, T. W., Overmyer, K. A., Cui, Y., Armstrong, E. A., Howell, P. R., Burhans, M. S., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-11945-9 · Cited by 55 · see citing works
Intracellular Acetyl CoA Potentiates the Therapeutic Efficacy of Antitumor CD8+ T Cells
Chowdhury, S., Kar, A., Bhowmik, D., Gautam, A., Basak, D., Sarkar, I., Ghosh, P., Sarkar, D., Deka, A., Chakraborty, P., et al. (2022) · Cancer Research · doi:10.1158/0008-5472.can-21-4052 · Cited by 55 · see citing works
ACLY: A biomarker of recurrence in breast cancer
Chen, Y., Li, K., Gong, D., Zhang, J., Li, Q., Zhao, G., & Lin, P. (2020) · Pathology - Research and Practice · doi:10.1016/j.prp.2020.153076 · Cited by 53 · see citing works
ATP citrate lyase inhibitor triggers endoplasmic reticulum stress to induce hepatocellular carcinoma cell apoptosis via p‐eIF2α/ATF4/CHOP axis
Zheng, Y., Zhou, Q., Zhao, C., Li, J., Yu, Z., & Zhu, Q. (2021) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.16235 · Cited by 53 · see citing works
N-acetylaspartate pathway is nutrient responsive and coordinates lipid and energy metabolism in brown adipocytes
Huber, K., Hofer, D., Trefely, S., Pelzmann, H. J., Madreiter‐Sokolowski, C. T., Duta-Mare, M., Schlager, S., Trausinger, G., Stryeck, S., Graier, W. F., et al. (2018) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2018.08.017 · Cited by 49 · see citing works
Self-citation
Global Profiling of Acetyltransferase Feedback Regulation
Montgomery, D. C., Garlick, J. M., Kulkarni, R. A., Kennedy, S., Allali‐Hassani, A., Kuo, Y., Andrews, A. J., Wu, H., Vedadi, M., & Meier, J. L. (2016) · Journal of the American Chemical Society · doi:10.1021/jacs.6b03036 · Cited by 48 · see citing works
Decreased expression of acetyl‐CoA synthase 2 promotes metastasis and predicts poor prognosis in hepatocellular carcinoma
Sun, L., Kong, Y., Cao, M., Zhou, H., Li, H., Cui, Y., Fang, F., Zhang, W., Li, J., Zhu, X., et al. (2017) · Cancer Science · doi:10.1111/cas.13252 · Cited by 47 · see citing works
Should we consider subcellular compartmentalization of metabolites, and if so, how do we measure them?
Wellen, K. E., & Snyder, N. W. (2019) · Current Opinion in Clinical Nutrition & Metabolic Care · doi:10.1097/mco.0000000000000580 · Cited by 45 · see citing works
Self-citation
Downregulation of acetyl-CoA synthetase 2 is a metabolic hallmark of tumor progression and aggressiveness in colorectal carcinoma
Bae, J. M., Kim, J. H., Oh, H. J., Park, H. E., Lee, T. H., Cho, N., & Kang, G. H. (2016) · Modern Pathology · doi:10.1038/modpathol.2016.172 · Cited by 44 · see citing works
Allosteric regulation of the biotin-dependent enzyme pyruvate carboxylase by acetyl-CoA
Adina-Zada, A., Zeczycki, T. N., Maurice, M. S., Jitrapakdee, S., Cleland, W. W., & Attwood, P. V. (2012) · Biochemical Society Transactions · doi:10.1042/bst20120041 · Cited by 42 · see citing works
Low expression of ACLY associates with favorable prognosis in acute myeloid leukemia
Wang, J., Ye, W., Yan, X., Guo, Q., Ma, Q., Lin, F., Huang, J., & Jin, J. (2019) · Journal of Translational Medicine · doi:10.1186/s12967-019-1884-5 · Cited by 42 · see citing works
Hyperinsulinemia promotes aberrant histone acetylation in triple-negative breast cancer
Senapati, P., Kato, H., Lee, M., Leung, A., Thai, C., Sanchez, A., Gallagher, E. J., LeRoith, D., Seewaldt, V. L., Ann, D. K., et al. (2019) · Epigenetics & Chromatin · doi:10.1186/s13072-019-0290-9 · Cited by 42 · see citing works
AMPK β1 reduces tumor progression and improves survival in p53 null mice
Houde, V. P., Donzelli, S., Sacconi, A., Galić, S., Hammill, J. A., Bramson, J. L., Foster, R. A., Tsakiridis, T. K., Kemp, B. E., Grasso, G., et al. (2017) · Molecular Oncology · doi:10.1002/1878-0261.12079 · Cited by 39 · see citing works
Rat mammary gland ATP‐citrate lyase is phosphorylated by cyclic AMP‐dependent protein kinase
Guy, P. S., Cohen, P., & Hardie, D. G. (1980) · FEBS Letters · doi:10.1016/0014-5793(80)81087-8 · Cited by 38 · see citing works
Advances into understanding metabolites as signaling molecules in cancer progression
Liu, J. Y., & Wellen, K. E. (2020) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2020.01.013 · Cited by 37 · see citing works
Self-citation
The interaction between the gut microbiota and dietary carbohydrates in nonalcoholic fatty liver disease
Park, G. S. H., Jung, S., Wellen, K. E., & Jang, C. (2021) · Experimental & Molecular Medicine · doi:10.1038/s12276-021-00614-x · Cited by 37 · see citing works
Self-citation
Paradoxical activation of transcription factor SREBP1c and de novo lipogenesis by hepatocyte-selective ATP-citrate lyase depletion in obese mice
Yenilmez, B., Kelly, M., Zhang, G., Wetoska, N., Ilkayeva, O., Min, K., Rowland, L. A., DiMarzio, C., He, W., Raymond, N., et al. (2022) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2022.102401 · Cited by 35 · see citing works
The mevalonate pathway is an actionable vulnerability of t(4;14)-positive multiple myeloma
Longo, J., Smirnov, P., Li, Z., Branchard, E., van Leeuwen, J. E., Licht, J. D., Haibe‐Kains, B., Andrews, D. W., Keats, J. J., Pugh, T. J., et al. (2020) · Leukemia · doi:10.1038/s41375-020-0962-2 · Cited by 34 · see citing works
Acetyl-CoA synthetase 2 enhances tumorigenesis and is indicative of a poor prognosis for patients with renal cell carcinoma
Zhang, S., He, J., Jia, Z., Yan, Z., & Yang, J. (2018) · Urologic Oncology Seminars and Original Investigations · doi:10.1016/j.urolonc.2018.01.013 · Cited by 31 · see citing works
A Systems Chemoproteomic Analysis of Acyl-CoA/Protein Interaction Networks
Levy, M. J., Montgomery, D. C., Sardiu, M. E., Montaño, J. L., Bergholtz, S. E., Nance, K. D., Thorpe, A. L., Fox, S. D., Lin, Q., Andrésson, Þ., et al. (2019) · Cell chemical biology · doi:10.1016/j.chembiol.2019.11.011 · Cited by 27 · see citing works
ACLY is the novel signaling target of PIP2/PIP3 and Lyn in acute myeloid leukemia
Basappa, J., Citir, M., Zhang, Q., Wang, H. Y., Liu, X., Melnikov, O., Yahya, H. A., Stein, F., Müller, R., Traynor‐Kaplan, A., et al. (2020) · Heliyon · doi:10.1016/j.heliyon.2020.e03910 · Cited by 27 · see citing works
Comparison of phospho- and dephospho-ATP citrate lyase
Ranganathan, N. S., Srere, P. A., & Linn, T. C. (1980) · Archives of Biochemistry and Biophysics · doi:10.1016/0003-9861(80)90006-5 · Cited by 26 · see citing works
Subcellular metabolic pathway kinetics are revealed by correcting for artifactual post harvest metabolism
Trefely, S., Liu, J., Huber, K., Doan, M. T., Jiang, H., Singh, J. P., von Krusenstiern, E. V., Bostwick, A., Xu, P. J., Bogner‐Strauß, J. G., et al. (2019) · Molecular Metabolism · doi:10.1016/j.molmet.2019.09.004 · Cited by 26 · see citing works
Self-citation
Effects of phosphorylation on the kinetic properties of rat liver ATP-citrate lyase
Houston, B., & Nimmo, H. G. (1985) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/0167-4889(85)90095-3 · Cited by 24 · see citing works
Structure of ACLY in complex with CoA
Wei, X., & Marmorstein, R. (2019) · Worldwide Protein Data Bank · doi:10.2210/pdb6poe/pdb · Cited by 24 · see citing works
Effect of Oxaloacetate and Phosphorylation on ATP-Citrate Lyase Activity
Pentyala, S., & Benjamin, W. B. (1995) · Biochemistry · doi:10.1021/bi00035a001 · Cited by 21 · see citing works
Identification and integrative analysis of ACLY and related gene panels associated with immune microenvironment reveal prognostic significance in hepatocellular carcinoma
Xu, Y., Zhang, Z., Xu, D., Yang, X. L., Zhou, L., & Zhu, Y. (2021) · Cancer Cell International · doi:10.1186/s12935-021-02108-2 · Cited by 20 · see citing works
NRF2/ACSS2 axis mediates the metabolic effect of alcohol drinking on esophageal squamous cell carcinoma
Odera, J. O., Xiong, Z., Huang, C. D., Gu, N., Yang, W., Githanga, J. N., Odera, E. O., Paiboonrungruang, C., & Chen, X. L. (2020) · Biochemical Journal · doi:10.1042/bcj20200452 · Cited by 16 · see citing works
Metabolic convergence on lipogenesis in RAS, BCR-ABL, and MYC-driven lymphoid malignancies
Liefwalker, D. F., Gabay, M., Wang, Z., Pathak, K. V., Plaisier, S. B., Shah, V. M., Babra, B., Dewson, G. S., Lai, I. K., Mosley, A. R., et al. (2021) · Cancer & Metabolism · doi:10.1186/s40170-021-00263-8 · Cited by 11 · see citing works
Myeloid-Specific Acly Deletion Alters Macrophage Phenotype In Vitro and In Vivo without Affecting Tumor Growth
de Goede, K. E., Verberk, S. G. S., Baardman, J., Harber, K. J., van Kooyk, Y., de Winther, M. P. J., Schetters, S. T. T., & den Bossche, J. V. (2021) · Cancers · doi:10.3390/cancers13123054 · Cited by 10 · see citing works

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Integrative metabolism in MASLD and MASH: Pathophysiology and emerging mechanisms
Steinberg, G. R., Valvano, C. M., De Nardo, W., & Watt, M. J. (2025) · Journal of Hepatology · doi:10.1016/j.jhep.2025.02.033 · Cited by 240 · see citing works
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 168 · see citing works
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 142 · see citing works
“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 134 · see citing works
“…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-citation
MASH: the nexus of metabolism, inflammation, and fibrosis
Steinberg, G. R., Carpentier, A., & Wang, D.-D. (2025) · Journal of Clinical Investigation · doi:10.1172/jci186420 · Cited by 110 · see citing works
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 119 · see citing works
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 109 · see citing works
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 107 · see citing works
“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 87 · see citing works
“…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].”
Background
Lipid metabolic reprograming: the unsung hero in breast cancer progression and tumor microenvironment
Wan, 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 92 · see citing works
“Acetyl-CoA is generated through the catabolism of glucose, fatty acids, ketone bodies, and proteins [60].”
Biochemistry and regulation of histone lysine l-lactylation
Sheng, X., Lin, H.-N., Cole, P. A., & Zhao, Y. (2025) · Nature reviews. Molecular cell biology · doi:10.1038/s41580-025-00876-7 · Cited by 105 · see citing works
“…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.”
Lactylation in cancer: Mechanisms in tumour biology and therapeutic potentials
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 · see citing works
“59 The production process for lactyl-CoA remains less well understood.”
Method
Cancer 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 67 · see citing works
Lipid metabolism as a target for cancer drug resistance: progress and prospects
Wang, Z., Wang, Y., Li, Z., Xue, W., Hu, S., & Kong, X. (2023) · Frontiers in Pharmacology · doi:10.3389/fphar.2023.1274335 · Cited by 66 · see citing works
“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.”
The crosstalk between metabolism and translation
Biffo, S., Ruggero, D., & Santoro, M. M. (2024) · Cell Metabolism · doi:10.1016/j.cmet.2024.07.022 · Cited by 63 · see citing works
PDHX acetylation facilitates tumor progression by disrupting PDC assembly and activating lactylation-mediated gene expression
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 · see citing works
“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.”
Sulfide regulation and catabolism in health and disease
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 56 · see citing works
“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).”
ACLY inhibition promotes tumour immunity and suppresses liver cancer
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 61 · see citing works
“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 · see citing works
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 54 · see citing works
“…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 · see citing works
“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].”
Background
A novel CPT1A covalent inhibitor modulates fatty acid oxidation and CPT1A-VDAC1 axis with therapeutic potential for colorectal cancer
Hu, 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 49 · see citing works
“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].”
Background
A two-way relationship between histone acetylation and metabolism
Charidemou, E., & Kirmizis, A. (2024) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2024.10.005 · Cited by 47 · see citing works
Decoding the metabolic dialogue in the tumor microenvironment: from immune suppression to precision cancer therapies
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 51 · see citing works
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 48 · see citing works
Activation of polyamine catabolism promotes glutamine metabolism and creates a targetable vulnerability in lung cancer
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 41 · see citing works
“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).”
Method
SOAT1 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 · see citing works
“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].”
Acetyl-CoA metabolic accumulation promotes hepatocellular carcinoma metastasis via enhancing CXCL1-dependent infiltration of tumor-associated neutrophils
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 41 · see citing works
Chemotherapy-induced acetylation of ACLY by NAT10 promotes its nuclear accumulation and acetyl-CoA production to drive chemoresistance in hepatocellular carcinoma
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 · see citing works
“The majority of acetyl-CoA is generated in the mitochondrial matrix, and powers the tricarboxylic acid (TCA) cycle and electron transport chain [18, 19].”
Background
Subcellular 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 42 · see citing works
“…(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).”
Background
The emerging intertwined activities of metabolism and epigenetics unveils culprits and prospects in cancer
Verma, A., & Lindroth, A. M. (2025) · Experimental & Molecular Medicine · doi:10.1038/s12276-025-01537-7 · Cited by 43 · see citing works
“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 .”
Cytosolic acetyl-coenzyme A is a signalling metabolite to control mitophagy
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 41 · see citing works
Lipid metabolism reprogramming in endometrial cancer: biological functions and therapeutic implications
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 · see citing works
“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].”
Background
Modulating lipid metabolism by nanoparticles (NPs)-mediated ACSL3 silencing to inhibit hepatocellular carcinoma growth and metastasis
Huang, 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 38 · see citing works
“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].”
Fatty Acid Oxidation Supports Lymph Node Metastasis of Cervical Cancer via Acetyl‐CoA‐Mediated Stemness
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 · see citing works
Inhibition of ACSS2 triggers glycolysis inhibition and nuclear translocation to activate SIRT1/ATG5/ATG2B deacetylation axis, promoting autophagy and reducing malignancy and chemoresistance in ovarian cancer
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 38 · see citing works
Brown fat ATP-citrate lyase links carbohydrate availability to thermogenesis and guards against metabolic stress
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 · see citing works
“…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-citation
Filtering cells with high mitochondrial content depletes viable metabolically altered malignant cell populations in cancer single-cell studies
Yates, J., Kraft, A., & Boeva, V. (2025) · Genome biology · doi:10.1186/s13059-025-03559-w · Cited by 35 · see citing works
“…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 35 · see citing works
“Subsequently, acetyl-CoA is metabolized by the TCA cycle to produce metabolites such as NADH and FADH2 [75].”
PTPRK regulates glycolysis and de novo lipogenesis to promote hepatocyte metabolic reprogramming in obesity
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 32 · see citing works
“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.”
SLC25A1 and ACLY maintain cytosolic acetyl-CoA and regulate ferroptosis susceptibility via FSP1 acetylation
Li, W., Han, J., Huang, B., Xu, T., Wan, Y., Luo, D. L., Kong, W., Yu, Y. H., Zhang, L., Nian, Y., et al. (2025) · The EMBO Journal · doi:10.1038/s44318-025-00369-5 · Cited by 32 · see citing works
“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).”
Nucleo-cytosolic acetyl-CoA drives tumor immune evasion by regulating PD-L1 in melanoma
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 · see citing works
Dissecting the anti-obesity components of ginseng: How ginseng polysaccharides and ginsenosides target gut microbiota to suppress high-fat diet-induced obesity
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 32 · see citing works
“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].”
The role of acetylation and deacetylation in cancer metabolism
Wang, C., & Ma, X. (2025) · Clinical and Translational Medicine · doi:10.1002/ctm2.70145 · Cited by 31 · see citing works
METTL14 promotes lipid metabolism reprogramming and sustains nasopharyngeal carcinoma progression via enhancing m6A modification of ANKRD22 mRNA
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 · see citing works
Disentangling the molecular mystery of tumour–microbiota interactions: Microbial metabolites
Duan, Y.-W., Dai, J.-H., Lu, Y.-Q., Qiao, H., & Liu, N. (2024) · Clinical and Translational Medicine · doi:10.1002/ctm2.70093 · Cited by 29 · see citing works
Simultaneous Engineering of the Thermostability and Activity of a Novel Aldehyde Dehydrogenase
Xu, K., Chen, Q., Fu, H., Chen, Q., Gu, J., Wang, X., & Zhou, J. (2025) · ACS Catalysis · doi:10.1021/acscatal.4c06840 · Cited by 29 · see citing works
Nanomaterial‐Triggered Ferroptosis and Cuproptosis in Cancer Therapy
Sahoo, S. S., & Manna, D. (2025) · Small · doi:10.1002/smll.202412462 · Cited by 28 · see citing works
The metabolism-immune axis in colorectal cancer: remodeling the tumor microenvironment through metabolite signaling
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 31 · see citing works
“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 27 · see citing works
“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.”
BackgroundInfluential
Lipid Metabolism Reprogramming in Cancer: Insights into Tumor Cells and Immune Cells Within the Tumor Microenvironment
Liu, R., Wang, C., Tao, Z., & Hu, G. (2025) · Biomedicines · doi:10.3390/biomedicines13081895 · Cited by 28 · see citing works
“Consequently, cancer cells cunningly utilize acetyl-CoA-associated metabolism to reprogram lipid metabolism, aggravating the tumorigenesis [65].”
Analysis of the effect of different withering methods on tea quality based on transcriptomics and metabolomics
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 · see citing works
α‐Lipoic Acid Ameliorates Arsenic‐Induced Lipid Disorders by Promoting Peroxisomal β‐Oxidation and Reducing Lipophagy in Chicken Hepatocyte
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 · see citing works
ACSS2 drives senescence-associated secretory phenotype by limiting purine biosynthesis through PAICS acetylation
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 25 · see citing works
“Acetyl-CoA, the lipogenic precursor and acetylation substrate, plays compartment-speci ﬁ c roles in physiological and pathological processes, including cellular senescence 35 .”
PSMD14 Stabilizes SLC7A11 to Ameliorate Glucocorticoid‐Induced Osteoporosis by Suppressing Osteocyte Ferroptosis
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 · see citing works
Dendritic cells: understanding ontogeny, subsets, functions, and their clinical applications
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 · see citing works
“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.”
Influential
Epigenetic remodelling under hypoxia
Verdikt, R., & Thienpont, B. (2023) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2023.10.005 · Cited by 23 · see citing works
SIRT4 Promotes Pancreatic Cancer Stemness by Enhancing Histone Lactylation and Epigenetic Reprogramming Stimulated by Calcium Signaling
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 23 · see citing works
Metabolites as signalling molecules in the tumour immune microenvironment
Mao, Y., Xia, W., & Jiang, P. (2026) · Nature reviews. Immunology · doi:10.1038/s41577-025-01258-y · Cited by 27 · see citing works
“The acetylation of proteins and DNA in tumour cells has been extensively studied and documented 154 .”
Oxidative stress-mediated epigenetic remodeling, metastatic progression and cell signaling in cancer
Phull, A. R., Arain, S. Q., Majid, A., Fatima, H., Ahmed, M., & Kim, S. J. (2024) · ONCOLOGIE · doi:10.1515/oncologie-2024-0157 · Cited by 22 · see citing works
Metabolic interventions combined with CTLA-4 and PD-1/PD-L1 blockade for the treatment of tumors: mechanisms and strategies
Liao, L., Xu, H., Zhao, Y., & Zheng, X. (2023) · Frontiers of Medicine · doi:10.1007/s11684-023-1025-7 · Cited by 22 · see citing works
Metabolic reprogramming in cancer: signaling pathways and therapeutic targets
Dong, S., & Lei, X. (2026) · Molecular Cancer · doi:10.1186/s12943-026-02582-0 · Cited by 28 · see citing works
“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 · see citing works
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 · see citing works
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 · see citing works
Epigenomic mapping reveals distinct B cell acute lymphoblastic leukemia chromatin architectures and regulators
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 21 · see citing works
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 · see citing works
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 · see citing works
“[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 20 · see citing works
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 19 · see citing works
“8b) 30–32 .”
Beyond energy: how TCA cycle-derived metabolites regulate gene expression and inflammation in the nucleus
Randhawa, J., & Pålsson‐McDermott, E. M. (2025) · Journal of Inflammation · doi:10.1186/s12950-025-00461-x · Cited by 21 · see citing works
“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].”
Beyond Bioenergetics: Emerging Roles of Mitochondrial Fatty Acid Oxidation in Stress Response and Aging
Bang, S., Choi, S.-H., & Jeong, S. M. (2025) · Cells · doi:10.3390/cells14241956 · Cited by 21 · see citing works
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 22 · see citing works
“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 · see citing works
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 · see citing works
TIGIT deficiency promotes autoreactive CD4+ T-cell responses through a metabolic‒epigenetic mechanism in autoimmune myositis
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 18 · see citing works
“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…”
Influential
Regulatory Role and Biomarker Potential of Gut Microbiota Metabolites in the Progression of Metabolic Dysfunction-Associated Steatotic Liver Disease to Hepatocellular Carcinoma
Che, Z., Xue, W., Zhao, X., Hu, C., & Tian, Y. (2025) · Clinical and Translational Gastroenterology · doi:10.14309/ctg.0000000000000914 · Cited by 18 · see citing works
“This may support tumor cell growth and survival under unfavorable conditions (71,72).”
ACAT2 suppresses the ubiquitination of YAP1 to enhance the proliferation and metastasis ability of gastric cancer via the upregulation of SETD7
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 · see citing works
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 · see citing works
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 · see citing works
“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 17 · see citing works
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 17 · see citing works
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 · see citing works
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 · see citing works
Phospholipid Biosynthesis: An Unforeseen Modulator of Nuclear Metabolism
Qiu, H., & Ye, C. (2025) · Biology of the Cell · doi:10.1111/boc.70002 · Cited by 16 · see citing works
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 · see citing works
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 · see citing works
Mechanism of intestinal microbiota disturbance promoting the occurrence and development of esophageal squamous cell carcinoma——based on microbiomics and metabolomics
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 · see citing works
“A lack of pantothenic acid and coenzyme A can lead to DNA loss and mutation, thereby increasing the risk of developing tumors [36].”
Background
A Graphene-Based Lipid Modulation Nanoplatform for Synergetic Lipid Starvation/Chemo/Photothermal Therapy of Oral Squamous Cell Carcinoma
Li, 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 · see citing works
“15 Therefore, inhibiting ACLY may downregulate acetyl-CoA levels in tumor cells, leading to decreased fatty acid and cholesterol production.”
Background
Metabolism Meets Translation: Dietary and Metabolic Influences on tRNA Modifications and Codon Biased Translation
Rashad, S., & Marahleh, A. (2025) · Wiley Interdisciplinary Reviews - RNA · doi:10.1002/wrna.70011 · Cited by 14 · see citing works
“…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
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Background
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Background

Acetyl-CoA metabolism as a therapeutic target for cancer
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Abstract IA24: Acetyl-CoA metabolism, gene regulation, and stress management
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Self-citation

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.
ORCID: Guertin, David A.
Wellen, Kathryn E.
Venue: Nature Reviews Cancer
Publisher: Springer Science and Business Media LLC
Published: 2023-01-19
Volume: 23
Issue: 3
Pages: 156-172
ISSN: 1474-175X (ISSN-L)
1474-1768
DOI: 10.1038/s41568-022-00543-5
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: cc-by
www.springernature.com/gp/researchers/text-and-data-mining (tdm)
www.springernature.com/gp/researchers/text-and-data-mining (vor)
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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