ACAT1在脂肪代谢、线粒体能量稳态中的多重角色:机制与疾病关联OA

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.