Document Detail

A mathematical model for the determination of steady-state cardiolipin remodeling mechanisms using lipidomic data.
MedLine Citation:
PMID:  21695174     Owner:  NLM     Status:  MEDLINE    
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 maximum likelihood approach to infer parameters, we found that for most samples the four chain positions have an independent and identical distribution, indicating they are remodeled by the same processes. Furthermore, for most brain samples and liver, the distribution of acyl chains is well-fit by a simple linear combination of the pools of acyl chains in phosphatidylcholine (PC), phosphatidylethanolamine (PE), and phosphatidylglycerol (PG). This suggests that headgroup chemistry is the key determinant of acyl donation into CL, with chain length/saturation less important. This canonical remodeling behavior appears damaged in some tumor samples, which display a consistent excess of CL molecules having particular masses. For heart and lung, the "proportional incorporation" assumption is not adequate to explain the CL distribution, suggesting additional acyl CoA-dependent remodeling that is chain-type specific. Our findings indicate that CL remodeling processes can be described by a small set of quantitative relationships, and that bioinformatic approaches can help determine these processes from high-throughput lipidomic data.
Lu Zhang; Robert J A Bell; Michael A Kiebish; Thomas N Seyfried; Xianlin Han; Richard W Gross; Jeffrey H Chuang
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2011-06-10
Journal Detail:
Title:  PloS one     Volume:  6     ISSN:  1932-6203     ISO Abbreviation:  PLoS ONE     Publication Date:  2011  
Date Detail:
Created Date:  2011-06-22     Completed Date:  2011-10-21     Revised Date:  2013-06-28    
Medline Journal Info:
Nlm Unique ID:  101285081     Medline TA:  PLoS One     Country:  United States    
Other Details:
Languages:  eng     Pagination:  e21170     Citation Subset:  IM    
Department of Biology, Boston College, Chestnut Hill, Massachusetts, United States of America.
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MeSH Terms
Cardiolipins / chemistry,  metabolism*
Computational Biology*
Fatty Acids / chemistry
Likelihood Functions
Mass Spectrometry
Models, Biological*
Reproducibility of Results
Reg. No./Substance:
0/Cardiolipins; 0/Fatty Acids

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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