The role of lipase maturation factor 1 in hypertriglyceridaemia and atherosclerosis: An update

Figures

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  Figure 1.. A model for the regulation and function of LMF1. ER stress regulates LMF1 expression in ATF6-dependent way. 38 LMF1-derived circular RNA negatively regulates miR-125a, which subsequently negatively regulates its downstream direct targets VEFGA and FGF1 – crucial players in atherosclerosis development. 39 Lipases (LPL, HL, and EL), fibronectin, and LDLR are known clients of LMF1, while other chaperones and disulphide bonds processing enzymes (ERp44, ERp72, ERdj5, calnexin, UGGT1, and UGGT2) directly interact with LMF1 and facilitate lipase maturation. 40 Hrd1 regulates Sel1L stability, while Sel1L interacts with and stabilises the LMF1-LPL complex. Negative regulation (red), positive regulation (black), indirect effect through several steps (dotted), direct interactions (blue), and LMF1 chaperone clients (dotted green double arrows). ER stress upregulates LMF1 (magenta arrow); treatment with the VSMCs proliferation and migration regulator PDGF-BB upregulates circLMF1, VEGFA, and FGF1 (cyan arrow), while downregulating miR-125a-3p (orange arrow). LMF1: lipase maturation factor 1; circLMF1: LMF1-derived circular RNA; miR: microRNA; LPL: lipoprotein lipase; HL: hepatic lipase; EL:…

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  Figure 2.. Schematic representation of LMF1’s topology, in vitro tested mutations, and conserved cysteine (C) residues.24–26,40 Mutations affecting lipases secretion/activity are depicted in red circles, mutations without significant effect on lipases are shown in yellow circles, and the only identified mutation that increases lipase activity, T143M, is depicted in magenta/green circle. Conserved C residues are shown in olive.