Review
Biochemistry & Molecular Biology
Weijing He, Qingguo Li, Xinxiang Li
Summary: Acetyl-CoA is an important molecule that participates in multiple intracellular metabolic reactions and affects protein post-translational modification, playing a key role in cell metabolism and epigenetic inheritance. In cancer, extensive lipid metabolism and histone acetylation are required for cancer cell growth and expression of cancer-promoting genes. Acetyl-CoA, as a raw material for lipid synthesis and histone acetylation, has a major impact on lipid metabolism and histone acetylation in cancer. Moreover, acetyl-CoA connects lipid metabolism with histone acetylation, forming a complex regulatory mechanism that influences cancer growth, proliferation, and metastasis.
BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER
(2023)
Review
Endocrinology & Metabolism
Gonzalo Fernandez-Fuente, Michael J. Rigby, Luigi Puglielli
Summary: By regulating intracellular signaling molecules, especially the citrate/acetyl-CoA pathway, homeostatic responses in cells can be activated. The citrate/acetyl-CoA pathway plays important roles in various biological functions within cells and is associated with N epsilon-lysine acetylation. Specifically, in the acetylation machinery of the endoplasmic reticulum (ER), ER acetylation regulates metabolic communication and homeostasis between different cellular organelles, affecting cellular adaptive responses and specific disease states. Therefore, citrate and acetyl-CoA should be recognized as both metabolic substrates and important signaling molecules for cellular adaptation.
MOLECULAR METABOLISM
(2023)
Article
Agriculture, Multidisciplinary
Xue-Ning Wang, Li-Li Hong, Jian-Qiang Kong
Summary: A stable acetyl-CoA-synthesizing biocatalyst was identified using maltose O-acetyltransferase (MAT) with diacerein as an acetyl donor, providing a promising and cost-effective alternative method for acetylation modifications. The mutant MAT-E125F showed the highest yield of acetyl-CoA production and could also synthesize glycosyl esters through acetylation or transesterification reactions. The multifunctional MAT displayed a potent capacity in synthesizing acetyl-CoA and glycosyl esters using diacerein as an acetyl donor.
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
(2021)
Article
Multidisciplinary Sciences
Sethu C. Nair, Justin T. Munro, Alexis Mann, Manuel Llinas, Sean T. Prigge
Summary: Coenzyme A (CoA) biosynthesis is a critical target for combating malaria. The study reveals the essential role of the mitochondrion in cellular acetyl-CoA biosynthesis and identifies a synthetic lethal relationship between two key ketoacid dehydrogenase enzymes. The lipoate attachment enzyme LipL2 is found to be crucial for the activity of these enzymes, which is indispensable for parasite survival due to its involvement in acetyl-CoA metabolism. Additionally, the study highlights the importance of mitochondrial-derived acetyl-CoA for protein acetylation outside the mitochondrion. Overall, these findings underscore the significance of the mitochondrion in cellular acetyl-CoA metabolism and protein acetylation crucial for parasite survival.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Review
Biochemistry & Molecular Biology
Patrick C. Bradshaw
Summary: Acetyl-CoA plays important roles in regulating gene expression and promoting longevity, with decreased cytoplasmic levels potentially contributing to longevity and increased nuclear levels aiding in histone acetylation and lifespan extension. Future research should focus on the role of nuclear acetyl-CoA and histone acetylation in controlling hypothalamic inflammation, a key driver of organismal aging.
Review
Cell Biology
Amel Mameri, Jacques Cote
Summary: The multisubunit NuA4/TIP60 complex is involved in various biological processes as a lysine acetyltransferase, chromatin modifying factor and gene co-activator. However, understanding of its molecular mechanisms is limited and contradictory, thus requiring further investigation. Recently, the identification of JAZF1 as a novel subunit linked to metabolic homeostasis has provided an exciting direction for exploring the role of NuA4/TIP60 in metabolism.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Review
Immunology
Monica Dominguez, Bernhard Bruene, Dmitry Namgaladze
Summary: Recent studies have shown the profound influence of metabolism on immune responses, particularly through epigenetic regulation of gene expression. ACLY plays a crucial role in the formation of cytosolic acetyl-CoA, supporting de novo lipogenesis and contributing to epigenetic regulation through histone acetylation. Alternative sources of acetyl-CoA also play a role in metabolic and epigenetic regulation in immune cells.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Oncology
Chaofan Fan, Shing Kam, Pierluigi Ramadori
Summary: Liver cancer is a prevalent cancer type globally with limited treatment options. Metabolic and epigenetic abnormalities play crucial roles in the development of liver cancer, influencing the resilience and adaptability of tumor cells.
Article
Multidisciplinary Sciences
Dongwen Que, Feimei Kuang, Rui Kang, Daolin Tang, Jiao Liu
Summary: Alkaliptosis is a newly discovered pH-dependent cell death used for tumor therapy. ACSS2, an acetate-activating enzyme, is identified as a positive regulator of alkaliptosis in human PDAC cells. ACSS2 expression is upregulated in response to the alkaliptosis activator JTC801, and knockdown of ACSS2 inhibits JTC801-induced cell death and alters cellular pH. These findings provide new insights into the metabolic basis of alkaliptosis and potential strategies for PDAC treatment.
SCIENTIFIC REPORTS
(2023)
Article
Genetics & Heredity
Wei Zheng, Luisa Tasselli, Tie-mei Li, Katrin F. Chua
Summary: The modulation of dynamic histone acetylation states is crucial for gene expression and chromatin structure. SIRT6 controls nuclear levels of ACLY and regulates the expression of tumor suppressive genes by affecting nuclear acetyl-CoA pools.
Article
Biochemistry & Molecular Biology
Narayanan Puthillathu Vasudevan, Dharmendra K. Soni, John R. Moffett, Jishnu K. S. Krishnan, Abhilash P. Appu, Sarani Ghoshal, Peethambaran Arun, John M. Denu, Thomas P. Flagg, Roopa Biswas, Aryan M. Namboodiri
Summary: The acetate activating enzyme Acss2 plays a role in matching cellular metabolism to current conditions and has regulatory functions in addition to its role in lipid synthesis. Using Acss2 knockout mice, this study investigated the roles of Acss2 in liver, brain, and adipose tissue and found dysregulation of numerous signaling pathways and cellular processes. The loss of Acss2 resulted in few changes in fatty acid constitution in these organ systems. Overall, this research demonstrates the organ-specific transcriptional regulatory patterns of Acss2 and its role as a regulatory enzyme.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Cell Biology
Daqian Xu, Fei Shao, Xueli Bian, Ying Meng, Tingbo Liang, Zhimin Lu
Summary: Key pathological signaling pathways regulate metabolic enzymes, giving them nonmetabolic functions. These aberrantly regulated metabolic enzymes play critical roles in governing cellular activities, promoting disease progression.
Article
Plant Sciences
Yue Lu, Qing Bu, Mingli Chuan, Xiaoyun Cui, Yu Zhao, Dao-Xiu Zhou
Summary: Chromatin modifications play a crucial role in shaping the epigenome and regulating gene expression during plant development and adaptation to environmental changes. The activities of chromatin modification enzymes are influenced by cellular metabolites, such as S-adenosyl-methionine, acetyl-CoA, alpha-ketoglutarate, and NAD(+). On the other hand, changes in the plant epigenome and activity of epigenetic regulators can impact cellular metabolism through regulation of metabolic enzymes. This review highlights recent advances in understanding the metabolic control of plant chromatin regulators and epigenomes, which contribute to plant adaptation to environmental stresses.
Article
Oncology
Xu Zhou, Yu Zhou, Weiqing Shao, Liang Hong, Ming Lu, Wenwei Zhu
Summary: Acetyl-CoA metabolic aberration is associated with ICC metastasis, and down-regulation of ACOT12 promotes ICC metastasis, suggesting ACOT12 as a prognostic marker and potential therapeutic target for ICC metastasis.
Article
Clinical Neurology
Michael J. Rigby, Nicola Salvatore Orefice, Alexis J. Lawton, Min Ma, Samantha L. Shapiro, Sue Y. Yi, Inca A. Dieterich, Alyssa Frelka, Hannah N. Miles, Robert A. Pearce, John Paul J. Yu, Lingjun Li, John M. Denu, Luigi Puglielli
Summary: N (epsilon)-lysine acetylation within the lumen of the endoplasmic reticulum is a protein quality control system that selects properly folded glycoproteins in the early secretory pathway. Overexpression of the endoplasmic reticulum acetyl-CoA transporter AT-1 leads to dendritic branching, spine formation, and an autistic-like phenotype. The upregulation of SLC25A1, a gene associated with autism spectrum disorder, helps maintain the cytosolic pool of acetyl-CoA.
