Acetyl-coenzyme A synthetase, cytoplasmic

Catalyzes the synthesis of acetyl-CoA from short-chain fatty acids (PubMed:10843999, PubMed:28003429, PubMed:28552616, PubMed:38369012, PubMed:39561764). Acetate is the preferred substrate (PubMed:10843999, PubMed:28003429, PubMed:38369012, PubMed:39561764). Can also utilize propionate with a much lower affinity (PubMed:38369012). Catalyzes the conversion of lactate into lactoyl-CoA (PubMed:39561764). Does not catalyze the conversion of butyrate or crotonate to their corresponding acyl-CoAs (PubMed:38369012). Nuclear ACSS2 promotes glucose deprivation-induced lysosomal biogenesis and autophagy, tumor cell survival and brain tumorigenesis (PubMed:28552616). Glucose deprivation results in AMPK-mediated phosphorylation of ACSS2 leading to its translocation to the nucleus where it binds to TFEB and locally produces acetyl-CoA for histone acetylation in the promoter regions of TFEB target genes thereby activating their transcription (PubMed:28552616). The regulation of genes associated with autophagy and lysosomal activity through ACSS2 is important for brain tumorigenesis and tumor survival (PubMed:28552616). Acts as a chromatin-bound transcriptional coactivator that up-regulates histone acetylation and expression of neuronal genes (By similarity). Can be recruited to the loci of memory-related neuronal genes to maintain a local acetyl-CoA pool, providing the substrate for histone acetylation and promoting the expression of specific genes, which is essential for maintaining long-term spatial memory (By similarity)