Year: 2022
Type: article
Abstract: Statins are a class of drug widely prescribed for the prevention of cardiovascular disease, with pleiotropic cellular effects. Statins inhibit HMG-CoA reductase (HMGCR), which converts the metabolite HMG-CoA into mevalonate. Recent discoveries have shown HMG-CoA is a reactive metabolite that can non-enzymatically modify proteins and impact their activity. Therefore, we predicted that inhibition of HMGCR by statins might increase HMG-CoA levels and protein modifications. Upon statin treatment, we observe a strong increase in HMG-CoA levels and modification of only a single protein. Mass spectrometry identifies this protein as fatty acid synthase (FAS), which is modified on active site residues and, importantly, on non-lysine side-chains. The dynamic modifications occur only on a sub-pool of FAS that is located near HMGCR and alters cellular signaling around the ER and Golgi. These results uncover communication between cholesterol and lipid biosynthesis by the substrate of one pathway inhibiting another in a rapid and reversible manner.
Source: Nature Communications
Language: English
Subfield: Cancer Research
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $5,890
Funders: U.S. Department of Health and Human Services, Ellison Medical Foundation, American Heart Association, Glenn Foundation for Medical Research, National Institutes of Health, School of Medicine, Duke University, National Institute on Aging, National Heart, Lung, and Blood Institute, NIH Office of the Director, National Institute of General Medical Sciences, National Institute of Diabetes and Digestive and Kidney Diseases
Awards: G1104101391, G1375492032, G2343786742, G2645538083, Studies on the Mechanisms by which SIRT5 Regulates Aging and Disease, Thermo Lumos Tribrid High-Resolution Accurate-Mass Tandem Mass Spectrometer, Pharmacological Sciences Training Program, Post-Translational and Epigenetic Control of Branched-Chain Amino Acid Metabolism, G4894565215, G5122285708, The Effects of a Novel Statin-Induced Protein Modification on Fatty Acid Synthase, G661780776, Studies on the impact of acetyl-cysteine on metabolism, G746502960, G7657979593, G89171726, G9000043894, G9000097840, G9000108924, G9000138291, Endocrinology and Metabolism Training Program, G950284202
OpenAlex ID: W4229452807