Ask about this productRelated genes to: ACSS2 antibody
- Gene:
- ACSS2 NIH gene
- Name:
- acyl-CoA synthetase short chain family member 2
- Previous symbol:
- ACAS2
- Synonyms:
- ACS, ACSA, AceCS, dJ1161H23.1
- Chromosome:
- 20q11.22
- Locus Type:
- gene with protein product
- Date approved:
- 2001-09-17
- Date modifiied:
- 2017-06-13
Related products to: ACSS2 antibody
Related articles to: ACSS2 antibody
- Histone acetylation depends on acetyl-CoA, a central metabolic intermediate linking nutrient availability to chromatin regulation. Beyond bulk acetyl-CoA abundance, accumulating evidence indicates that chromatin-proximal acetyl-CoA production and acetate recycling provide spatial control over histone acetylation. In budding yeast, acetyl-CoA synthetase Acs2 supports nucleocytosolic acetyl-CoA production and associates with chromatin during transcriptional transitions, enabling local acetyl-CoA generation for histone acetyltransferases. Its mammalian ortholog, ACSS2, can accumulate in the nucleus in response to metabolic or signaling cues, where it recaptures acetate released by histone deacetylation to sustain promoter-localized histone acetylation. Acs2/ACSS2 also function within multi-enzyme or chromatin-associated assemblies, such as the yeast SESAME complex, coupling acetate metabolism with other metabolic and epigenetic pathways. These mechanisms influence gene expression, heterochromatin maintenance, senescence, and tumor-associated transcriptional programs. Together, these findings support a spatial model in which local metabolite production shapes epigenetic output independently of bulk metabolite abundance. Defining how such nuclear metabolic microenvironments are established and regulated may refine our understanding of metabolic control of chromatin and inform more selective therapeutic strategies. - Source: PubMed
Publication date: 2026/09/29
Kim JueunHe FeiLi ShanshanLee Jung-Shin - Emerging evidence has redefined metabolic reprogramming in hepatic stellate cells (HSCs) from a mere energy-supporting process to an active driver of liver fibrosis. Unlike conventional descriptions that focus on isolated pathway alterations, recent advances show that activated HSCs coordinate a multi-layered metabolic remodeling involving glucose, lipid, and amino acid networks. This review highlights three paradigm-shifting insights. First, glycolytically derived lactate not only serves as a metabolic byproduct but also acts as an epigenetic signal through histone lactylation, Which may contribute to the maintenance of fibrogenic gene expression. Second, metabolic crosstalk-exemplified by GLUT1-containing exosomes released from activated HSCs that reprogram quiescent neighboring cells-has been reported to mediate intercellular propagation of the fibrotic phenotype. Third, HSC activation is characterized by stage-specific metabolic vulnerabilities: early lipophagy supports fatty acid oxidation, whereas fully activated HSCs transition to a unique "dual hypermetabolic" state featuring concurrent glycolysis and tricarboxylic acid cycle engagement. Translational efforts have moved beyond single-pathway inhibition toward restoring metabolic homeostasis, with clinical-stage agents such as EVT0185 (a dual ACLY/ACSS2 inhibitor), VDR agonists, and ROCK2 inhibitors showing early promise. We propose that future anti-fibrotic strategies should prioritize stage-specific metabolic signatures, dynamic metabolomics-guided trial design, and the development of highly selective metabolic modulators that reverse, rather than merely block, HSCs activation. A metabolism-centric approach may provide a promising therapeutic direction for the management of chronic liver disease. - Source: PubMed
Publication date: 2026/09/07
Lu XinyuLi Zilong - Heart failure is often accompanied by metabolic remodeling; however, the contribution of compartment-specific acetyl-CoA homeostasis to mitochondrial dysfunction remains unclear. Here, we identify acetyl-CoA synthetase 2 (ACSS2) as an important regulator of cytosolic acetyl-CoA homeostasis and mitochondrial integrity under chronic β-adrenergic stress. Chronic isoproterenol stimulation induced heart failure with reduced ejection fraction in mice and selectively suppressed myocardial ACSS2 expression, resulting in depletion of cytosolic acetyl-CoA without altering total cellular levels. Similar changes were observed in H9c2 cardiomyoblasts exposed to prolonged β-adrenergic stimulation. Genetic deletion of ACSS2 recapitulated this metabolic disturbance, leading to mitochondrial structural remodeling and impaired oxidative respiration without evidence of altered mitochondrial biogenesis. Mechanistically, ACSS2 deficiency was associated with compartment-specific alterations in protein acetylation, characterized by reduced cytosolic acetylation and increased mitochondrial acetylation. Mitochondrial dysfunction was reversible, as long-term supplementation with butyrate restored mitochondrial respiratory capacity. Conversely, cardiomyocyte-targeted ACSS2 overexpression preserved cytosolic acetyl-CoA levels and was associated with improved mitochondrial respiratory function and attenuated cardiac dysfunction in vivo under chronic β-adrenergic stress. Together, these findings suggest that ACSS2-dependent cytosolic acetyl-CoA homeostasis contributes to the maintenance of mitochondrial quality and cardiac resilience, highlighting the importance of metabolic compartmentalization in heart failure pathophysiology. - Source: PubMed
Publication date: 2026/08/17
Sekine ToranosukeMiura ShunsukeMisaka TomofumiOkochi SatoshiOgawara RyoIchimura ShoheiYokokawa TetsuroOikawa MasayoshiWaguri SatoshiIshida TakafumiTakeishi Yasuchika - Dairy goats sustain milk production across marginal environments worldwide, yet genetic improvement of milk yield and composition remains slower than in cattle, constrained by smaller reference populations and limited functional validation. This review consolidates current evidence on the genes and polymorphisms governing milk production traits in dairy goats. Whole-genome resequencing and selection-signature scans repeatedly recover a lipogenic-somatotropic core (, , , , ), whereas genome-wide association studies (GWASs) confirm the casein cluster (, , , ) as the most reproducible determinant of protein content and as the principal fat-content gene. Transcriptomic, single-cell, and metabolomic analyses, together with functional dissection in goat mammary epithelial cells, resolve the regulatory networks-, , , and non-coding RNAs-that translate genotype into phenotype. Integrating multi-omic evidence with expanded, well-phenotyped populations is essential to convert this expanding catalog into precise marker-assisted and genomic selection for milk yield and quality. - Source: PubMed
Publication date: 2026/08/13
Wu ShuaishuaiTharwat MohamedUllah AbdNassar NourhanAlkheraif Abdulrahman AKhan Muhammad Zahoor - Inflammation is a pivotal driver of the progression from metabolic dysfunction-associated steatotic liver disease (MASLD) to metabolic dysfunction-associated steatohepatitis (MASH), an aggressive form associated with substantial liver-related mortality. However, the molecular mechanisms underlying the initiation and persistence of liver inflammation remain poorly defined. Here, we demonstrated a previously unrecognized role for hepatic acetyl-CoA synthetase short-chain family member 2 (ACSS2) in MASH, showing that ACSS2 upregulation in patients exacerbates MASH progression by functioning as an epigenetic regulator, independent of its canonical lipogenic role. Mechanistically, ACSS2, in complex with lysine acetyltransferase 5 (KAT5), upregulates allograft inflammatory factor-1 (AIF1) transcription via histone crotonylation, thereby inducing liver inflammation and subsequently resulting in the aberrant accumulation of senescent hepatocytes, which further enhances proinflammatory cytokine production. This ultimately initiates a vicious cycle of chronic inflammation, which directly promotes the progression from simple steatosis to MASH. Thus, our work reveals a mechanistically defined and pivotal role for ACSS2 in promoting the MASLD-to-MASH transition, highlighting its potential as a compelling therapeutic target. - Source: PubMed
Publication date: 2026/07/25
Wen XiaoWu KeyanWang MengyaoMa ZihanWang TaoZhang JingWang BeiChen SiyuanWang JingyiChen SiyueYang FanLiu ChuweiChen XianyangDeng LuCheng YafanMiao Qing RobertSun BaofaRuan XiongzhongLi KaiDuan YajunHu Wenquan