a mathematical model for the determination of steady-state cardiolipin remodeling mechanisms using lipidomic data数学模型的确定稳态心磷脂使用lipidomic数据重构机制.pdfVIP

A Mathematical Model for the Determination of Steady-State Cardiolipin Remodeling Mechanisms Using Lipidomic Data 1. 2. 3 1 4 Lu Zhang , Robert J. A. Bell , Michael A. Kiebish , Thomas N. Seyfried , Xianlin Han , Richard W. 3 1 Gross , Jeffrey H. Chuang * 1 Department of Biology, Boston College, Chestnut Hill, Massachusetts, United States of America, 2 Department of Biomedical Sciences, University of California San Francisco, San Francisco, California, United States of America, 3 Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri, United States of America, 4 Diabetes and Obesity Research Center, Sanford-Burnham Medical Research Institute, Orlando, Florida, United States of America Abstract Technical advances in lipidomic analysis have generated tremendous amounts of quantitative lipid molecular species data, whose value has not been fully explored. We describe a novel computational method to infer mechanisms of de novo lipid synthesis and remodeling from lipidomic data. We focus on the mitochondrial-specific lipid cardiolipin (CL), a polyglycerol phospholipid with four acyl chains. The lengths and degree of unsaturation of these acyl chains vary across CL molecules, and regulation of these differences is important for mitochondrial energy metabolism. We developed a novel mathematical approach to determine mechanisms controlling the steady-state distribution of acyl chain combinations in CL . We analyzed mitochondrial lipids from 18 types of steady-state samples, each with at least 3 replicates, from mouse brain, heart, lung, liver, tumor cells, and tumors grown in vitro. Using a mathematical model for the CL remodeling mechanisms and a