Dynamic simulation of cardiolipin remodeling: Greasing the wheels for an interpretative approach to lipidomics

Michael A. Kiebish, Rob Bell, Kui Yang, Toan Phan, Zhongdan Zhao, William Ames, Thomas N. Seyfried, Richard W. Gross, Jeffrey H. Chuang, Xianlin Han

Research output: Contribution to journalArticle

47 Scopus citations

Abstract

Cardiolipin is a class of mitochondrial specific phospholipid, which is intricately involved in mitochondrial functionality. Differences in cardiolipin species exist in a variety of tissues and diseases. It has been demonstrated that the cardiolipin profile is a key modulator of the functions of many mitochondrial proteins. However, the chemical mechanism(s) leading to normal and/or pathological distribution of cardiolipin species remain elusive. Herein, we describe a novel approach for investigating the molecular mechanism of cardiolipin remodeling through a dynamic simulation. This approach applied data from shotgun lipidomic analyses of the heart, liver, brain, and lung mitochondrial lipidomes to model cardiolipin remodeling, including relative content, regiospecificity, and isomeric composition of cardiolipin species. Generated cardiolipin profiles were nearly identical to those determined by shotgun lipidomics. Importantly, the simulated isomeric compositions of cardiolipin species were further substantiated through product ion analysis. Finally, unique enzymatic activities involved in cardiolipin remodeling were assessed from the parameters used in the dynamic simulation of cardiolipin profiles. Collectively, we described, verified, and demonstrated a novel approach by integrating both lipidomic analysis and dynamic simulation to study cardiolipin biology.jlr We believe this study provides a foundation to investigate cardiolipin metabolism and bioenergetic homeostasis in normal and disease states.

Original languageEnglish
Pages (from-to)2153-2170
Number of pages18
JournalJournal of lipid research
Volume51
Issue number8
DOIs
StatePublished - Aug 1 2010

Keywords

  • Barth syndrome
  • Bioinformatics
  • Shotgun lipidomics

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    Kiebish, M. A., Bell, R., Yang, K., Phan, T., Zhao, Z., Ames, W., Seyfried, T. N., Gross, R. W., Chuang, J. H., & Han, X. (2010). Dynamic simulation of cardiolipin remodeling: Greasing the wheels for an interpretative approach to lipidomics. Journal of lipid research, 51(8), 2153-2170. https://doi.org/10.1194/jlr.M004796