Endoplasmic reticulum quality control in lipoprotein metabolism

• Published in: Molecular and cellular endocrinology 2019-12, Vol.498, p.110547-110547, Article 110547
• Main Authors: Koerner, Cari M., Roberts, Benjamin S., Neher, Saskia B.
• Format: Article
• Language: English
• Subjects: ER quality control; LDLR; Lipid metabolism; Lipoprotein; LPL
• ISSN: 0303-7207; 1872-8057
• DOI: 10.1016/j.mce.2019.110547

Lipids play a critical role in energy metabolism, and a suite of proteins is required to deliver lipids to tissues. Several of these proteins require an intricate endoplasmic reticulum (ER) quality control (QC) system and unique secondary chaperones for folding. Key examples include apolipoprotein B (apoB), which is the primary scaffold for many lipoproteins, dimeric lipases, which hydrolyze triglycerides from circulating lipoproteins, and the low-density lipoprotein receptor (LDLR), which clears cholesterol-rich lipoproteins from the circulation. ApoB requires specialized proteins for lipidation, dimeric lipases lipoprotein lipase (LPL) and hepatic lipase (HL) require a transmembrane maturation factor for secretion, and the LDLR requires several specialized, domain-specific chaperones. Deleterious mutations in these proteins or their chaperones may result in dyslipidemias, which are detrimental to human health. Here, we review the ER quality control systems that ensure secretion of apoB, LPL, HL, and LDLR with a focus on the specialized chaperones required by each protein. •Lipids are an important macronutrient, and appropriate distribution of lipids to tissues in the body is necessary for health.•Some lipoproteins, lipases and receptors key to lipid metabolism have extraordinary ER folding and quality control needs.•Some of the key players in lipoprotein metabolism require specialized and general chaperones, to fold and exit the ER.Mutations that affect ER procesing of key players in lipoprotein metabolism link protein quality control with dyslipidemia.