Identifying novel microproteins and protein translation mechanisms involved in the development of atherosclerosis

University Of California-Irvine, Irvine CA

Investigators

Abstract

PROJECT SUMMARY/ABSTRACT Bile acids have been implicated as a contributor to atherosclerosis and is commonly found to be elevated in patients with metabolic disorders and cardiovascular disease (CVD). Recently, we observed extrahepatic bile acid release in high-fat/high-sucrose (HFHS) fed and LDLR KO pig models of atherosclerosis. To reveal novel targets to treat BA abnormality in patients with CVD, we aim to use the deep-sequencing technique, ribosome profiling (ribo-seq), to investigate translational control of BA synthesizing and trafficking genes in colon, kidney, liver, and muscle in HFHS-fed and LDLR KO atherogenic pig models (Aim 1). Additionally, Ribo-seq can be used to identify small open reading frames (smORFs) which encode microprotiens. These microprotiens are often overlooked and underappreciated as key players in biology and are highly enriched in mitochondria and often found to perturb metabolic processes. Thus, we aim to filter Ribo-seq data for smORFs encoding mitochondrial microproteins and determine their impacts on cellular metabolism using untargeted metabolomics/lipidomics followed by relevant stable isotope tracing to identify affected enzymes/pathways.