2.3.3.8	evolution	structural studies unmask a fundamental evolutionary relationship that links citrate synthase, the first enzyme of the oxidative Krebs cycle, to an ancestral tetrameric citryl-CoA lyase module that operates in the reverse Krebs cycle. This molecular transition marked a key step in the evolution of metabolism on Earth	757804	
2.3.3.8	malfunction	ATP citrate lyase knockdown induces proliferation arrest, cell-cycle arrest, and apoptosis in cancer cells and results in elevated expression of acyl-CoA synthetase short-chain family member 2	720439	
2.3.3.8	malfunction	ATP citrate lyase silencing impairs myoblast and satellite cell differentiation, and it is accompanied by a decrease in fast myosin heavy chain isoforms and MYOD	756395	
2.3.3.8	malfunction	decrease in ATP level, energy charge, and fatty acid content in mutant edt1 anthers	758054	
2.3.3.8	malfunction	deletion of the enzyme results in a complete loss of self and female fertility as well as a reduction in asexual reproduction, virulence, and trichothecene production. Although lipid synthesis is not affected by enzyme deletion, histone acetylation is dramatically reduced in the enzyme deletion mutants during sexual development	-, 719545	
2.3.3.8	malfunction	enzyme activity inhibition as well as gene silencing lead to reduced nitric oxide, reactive oxygen species and prostaglandin E2 inflammatory mediators	735597	
2.3.3.8	malfunction	enzyme inactivation decreases fatty acid synthesis by 60 to 80%	735713	
2.3.3.8	malfunction	enzyme knockdown triggers cellular senescence and activation of tumor suppressor p53	736093	
2.3.3.8	malfunction	inhibition of the enzyme suppresses in vitro glioblastoma cell migration, clonogenicity and brain invasion under glycolytic conditions and enhances the suppressive effects of a Met inhibitor on cell migration	704077	
2.3.3.8	malfunction	loss of ATP-citrate lyase results in severe developmental effects, with the production of asexual spores (conidia) being greatly reduced and a complete absence of sexual development	-, 719383	
2.3.3.8	malfunction	overexpression of the enzyme is observed in nonalcoholic fatty liver disease. Increased enzyme activity is associated with hypocituria, nonalcoholic fatty liver disease, and tumor cell growth. Decreased enzyme activity is associated with type 2 diabetes. ACLY knockdown or inhibition leads to a decrease in glucose-induced insulin secretion	718760	
2.3.3.8	malfunction	siRNA knockdown of ATP citrate lyase limits cancer cell proliferation and reduces cancer stemness	756645	
2.3.3.8	malfunction	upon genetic deletion of Acly, the gene coding for ATP-citrate lyase, cells remain viable and proliferate, although at an impaired rate. In the absence of ACLY, cells upregulate ACSS2 and utilize exogenous acetate to provide acetyl-CoA for de novo lipogenesis and histone acetylation. A physiological level of acetate is sufficient for cell viability and abundant acetyl-CoA production, although histone acetylation levels remain low in ACLY-deficient cells unless supplemented with high levels of acetate. ACLY-deficient adipocytes accumulate lipid in vivo, exhibit increased acetyl-CoA and malonyl-CoA production from acetate, and display some differences in fatty acid content and synthesis. Engagement of acetate metabolism is a crucial, although partial, mechanism of compensation for ACLY deficiency	756391	
2.3.3.8	metabolism	acetyl-coenzyme A (acetyl-CoA) generated by ATP citrate lyase (ACL) is utilized to acetylate histone H3 at MyoD regulatory regions, resulting in increased MyoD expression and improved muscle regeneration after injury	758518	
2.3.3.8	metabolism	ATP citrate lyase is an important enzyme linking carbohydrate to lipid metabolism by generating acetyl-CoA from citrate for fatty acid and cholesterol biosynthesis	758267	
2.3.3.8	metabolism	ATP-citrate lyase is a central metabolic enzyme. The acetyl-CoA product is crucial for the metabolism of fatty acids, the biosynthesis of cholesterol, and the acetylation and prenylation of proteins	757803	
2.3.3.8	metabolism	DNA methyltransferase 1 is regulated by ATP-citrate lyase	736797	
2.3.3.8	metabolism	enzyme in the de novo lipogenesis pathway. The enzyme is required for low molecular weight cyclin E-mediated transformation, migration, and invasion of breast cancer cells in vitro along with tumor growth in vivo	756335	
2.3.3.8	metabolism	essential enzyme for generating acetyl-CoA, a key metabolite for the first step in fatty acid synthesis and for histone acetylation. Regulation of the enzyme activity is a potentially important point of control for cell cycle regulation in the myeloid lineage	756281	
2.3.3.8	metabolism	involved in lung cancer pathogenesis	703014	
2.3.3.8	metabolism	modulation of ACLY expression correlates with the development and progressions of various chronic diseases such as neurodegenerative diseases, cardiovascular diseases, diabetes, obesity, inflammation, and cancer. Inhibition of ACLY activity modulates the glycolysis and lipogenesis processes and stimulates normal physiological functions	757453	
2.3.3.8	metabolism	regulatory role of ACLY activity in chondrocyte matrix homeostasis by modulation of the nucleocytosolic pool of acetyl-CoA, which impacted on catabolic and anabolic responses via post-translational and epigenetic modifications. Increased ACLY activity in osteoarthritis chondrocytes increases nucleocytosolic acetyl-CoA, leading to increased matrix catabolism via dysregulated histone and transcription factor acetylation	757200	
2.3.3.8	metabolism	the enzyme catalyzes the formation of cytosolic acetyl CoA, the starting material for de novo lipid and cholesterol biosynthesis	756189	
2.3.3.8	metabolism	the enzyme controls a glucose-to-acetate metabolic switch	756391	
2.3.3.8	metabolism	the enzyme is a major source of nucleocytosolic acetyl-CoA, a fundamental building block of carbon metabolism in eukaryotes	757232	
2.3.3.8	metabolism	the enzyme is an epigenetic regulator that promotes renal ectopic lipid accumulation and fibrogenesis leading to renal injury in obesity. Induction of ATP-citrate lyase in in the kidney of overweight or obese patients with chronic kidney disease is associated with increased ectopic lipid accumulation, glomerulosclerosis, and albuminuria. Acetyl-CoA is the substrate for de novo lipogenesis as well as for histone acetylation. By raising acetyl-CoA concentration ATP-citrate lyase promotes H3K9/14 and H3K27 hyperacetylation leading to up-regulation of several rate-limiting lipogenic enzymes and fibrogenic factors. On the other hand, the excess acetyl-CoA generated as a result of ATP-citrate lyase induction provides the substrate for these lipogenic enzymes to drive de novo lipogenesis leading to ectopic lipid accumulation, a detrimental event toward renal injury	756693	
2.3.3.8	metabolism	the enzyme is involved in citrate metabolism	718760	
2.3.3.8	metabolism	the enzyme links carbohydrate and lipid metabolism	757804	
2.3.3.8	metabolism	the enzyme links energy metabolism provided by catabolic pathways to biosynthesis. ACLY plays a pivotal role in cancer metabolism through the potential deprivation of cytosolic citrate, a process promoting glycolysis through the enhancement of the activities of PFK 1 and 2 with concomitant activation of oncogenic drivers such as PI3K/AKT which activate ACLY and the Warburg effect in a feed-back loop	756333	
2.3.3.8	metabolism	the enzyme plays a critical role in epigenetic regulation of diabetic renal fibrosis. It is essential for high glucose-induced histone hyperacetylation and fibrogenic gene upregulation in mesangial cells	755769	
2.3.3.8	metabolism	the enzyme plays a critical role in generating cytosolic acetyl CoA, a key building block for de novo fatty acid and cholesterol biosynthesis	756645	
2.3.3.8	metabolism	the enzyme plays an essential role in fatty acid synthesis	735713	
2.3.3.8	metabolism	the enzyme synthesizes cytosolic acetyl coenzyme A (acetyl-CoA), a fundamental cellular building block	757794	
2.3.3.8	physiological function	ATP citrate lyase is a positive regulator of glycolytic function in glioblastomas	704077	
2.3.3.8	physiological function	ATP citrate lyase is required for normal sexual and asexual development in Gibberella zeae	-, 719545	
2.3.3.8	physiological function	ATP citrate lyase plays a key role in regulating mitochondrial function, as well as glucose and lipid metabolism in skeletal muscle. The enzyme increases myoblast and satellite cell differentiation in vitro. It increases MYOD expression by acetyl-H3(K9/14/27) enrichment at the MYOD promoter. It acts downstream of IGF-1 to stimulate myogenesis. IT improves muscle regeneration following cardiotoxin-induced injury	756395	
2.3.3.8	physiological function	ATP-citrate lyase is required for development in Aspergillus nidulans	-, 719383	
2.3.3.8	physiological function	enzyme overexpression in Arabidopsis is associated with a 30% increase in wax on stems, while overexpression of a chimeric homomeric enzyme in the laticifer of roots of dandelion leads to a 4 and 2fold increase in rubber and triterpene content, respectively	736996	
2.3.3.8	physiological function	isoforms Acl1 and Acl2 coordinately modulate the cytoplasmic acetyl-CoA levels to regulate growth, development, and citric acid synthesis in Aspergillus niger	-, 736591	
2.3.3.8	physiological function	the enzyme (EDT1) is involved in the tapetum programmed cell death process	758054	
2.3.3.8	physiological function	the enzyme is essential for macrophage inflammatory response	735597	
2.3.3.8	physiological function	the enzyme is essentially required for embryonic development. Increased enzyme activity is found in the fetal development of the brain	718760	
2.3.3.8	physiological function	the enzyme regulates cellular senescence via an AMPK- and p53-dependent pathway	736093	
2.3.3.8	physiological function	the enzyme regulates mitochondrial function and cardiolipin synthesis and content in skeletal muscle	735902