Qu Mengyuan, Zhou Xuan, Wang Xiaotong, Li Honggang
Institute of Reproductive Health/Center of Reproductive Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
National Clinical Research Center for Infectious Disease; Department of liver Diseases, Shenzhen Third People's Hospital, Shenzhen, China.
Int J Biol Sci. 2021 Oct 11;17(15):4223-4237. doi: 10.7150/ijbs.64046. eCollection 2021.
Lipid metabolites are emerging as pivotal regulators of protein function and cell signaling. The availability of intracellular fatty acid is tightly regulated by glycolipid metabolism and may affect human body through many biological mechanisms. Recent studies have demonstrated palmitate, either from exogenous fatty acid uptake or fatty acid synthesis, may serve as the substrate for protein palmitoylation and regulate protein function via palmitoylation. Palmitoylation, the most-studied protein lipidation, encompasses the reversible covalent attachment of palmitate moieties to protein cysteine residues. It controls various cellular physiological processes and alters protein stability, conformation, localization, membrane association and interaction with other effectors. Dysregulation of palmitoylation has been implicated in a plethora of diseases, such as metabolic syndrome, cancers, neurological disorders and infections. Accordingly, it could be one of the molecular mechanisms underlying the impact of palmitate metabolite on cellular homeostasis and human diseases. Herein, we explore the relationship between lipid metabolites and the regulation of protein function through palmitoylation. We review the current progress made on the putative role of palmitate in altering the palmitoylation of key proteins and thus contributing to the pathogenesis of various diseases, among which we focus on metabolic disorders, cancers, inflammation and infections, neurodegenerative diseases. We also highlight the opportunities and new therapeutics to target palmitoylation in disease development.
脂质代谢产物正逐渐成为蛋白质功能和细胞信号传导的关键调节因子。细胞内脂肪酸的可用性受到糖脂代谢的严格调控，并可能通过多种生物学机制影响人体。最近的研究表明，无论是来自外源性脂肪酸摄取还是脂肪酸合成的棕榈酸酯，都可能作为蛋白质棕榈酰化的底物，并通过棕榈酰化调节蛋白质功能。棕榈酰化是研究最多的蛋白质脂化作用，包括棕榈酸酯部分与蛋白质半胱氨酸残基的可逆共价连接。它控制各种细胞生理过程，并改变蛋白质的稳定性、构象、定位、膜结合以及与其他效应器的相互作用。棕榈酰化失调与多种疾病有关，如代谢综合征、癌症、神经疾病和感染。因此，它可能是棕榈酸酯代谢产物影响细胞稳态和人类疾病的分子机制之一。在此，我们探讨脂质代谢产物与通过棕榈酰化调节蛋白质功能之间的关系。我们综述了棕榈酸酯在改变关键蛋白质的棕榈酰化从而导致各种疾病发病机制中假定作用的当前进展，其中我们重点关注代谢紊乱、癌症、炎症和感染、神经退行性疾病。我们还强调了在疾病发展过程中针对棕榈酰化的机会和新疗法。
