关键词: ACAT1, 胆固醇代谢, 线粒体稳态, 疾病关联, 治疗靶点, 猪

Abstract: The ACAT1 gene is located on human chromosome 11q22.3, comprising 16 exons. It encodes a protein that exists as homodimers or tetramers. The monomer contains nine transmembrane helices, with a histidine residue serving as the catalytic core. The central hydrophobic cavity of the tetramer may mediate cholesterol transport. This protein localizes to the endoplasmic reticulum, mitochondria, and mitochondria-endoplasmic reticulum contact sites (MAMs), with enrichment in liver and adipose tissue. The expression of ACAT1 is co-regulated by transcription factors, cholesterol levels, and epigenetic factors. In lipid metabolism, ACAT1 catalyzes the esterific ation of free cholesterol with long-chain fatty acids for storage, regulates adipocyte differentiation and brown fat maturation. In the study of pigs, SNP differences in ACAT1 are associated with fat deposition. In mitochondrial energy homeostasis, ACAT1 participates in acetyl-CoA metabolism, where acetylation regulates glycolysis and lipid metabolism, influencing mitochondrial function and ER-mitochondrial interactions. Abnormal ACAT1 expression is associated with diseases such as atherosclerosis (promoting foam cell formation) and tumors (regulating proliferation and immune evasion). Its inhibitors (e.g., avastimib, nevanimibe) exhibit antitumor activity, with some entering clinical trials. Targeting ACAT1 holds promise as a novel therapeutic strategy for related diseases.

Key words: ACAT1, cholesterol metabolism, mitochondrial homeostasis, disease association, therapeutic target, pig