Molecular structural diversity of mitochondrial cardiolipins

Proc Natl Acad Sci U S A. 2018 Apr 17;115(16):4158-4163. doi: 10.1073/pnas.1719407115. Epub 2018 Apr 4.

Abstract

Current strategies used to quantitatively describe the biological diversity of lipids by mass spectrometry are often limited in assessing the exact structural variability of individual molecular species in detail. A major challenge is represented by the extensive isobaric overlap present among lipids, hampering their accurate identification. This is especially true for cardiolipins, a mitochondria-specific class of phospholipids, which are functionally involved in many cellular functions, including energy metabolism, cristae structure, and apoptosis. Substituted with four fatty acyl side chains, cardiolipins offer a particularly high potential to achieve complex mixtures of molecular species. Here, we demonstrate how systematically generated high-performance liquid chromatography-mass spectral data can be utilized in a mathematical structural modeling approach, to comprehensively analyze and characterize the molecular diversity of mitochondrial cardiolipin compositions in cell culture and disease models, cardiolipin modulation experiments, and a broad variety of frequently studied model organisms.

Keywords: cardiolipin; lipids; mass spectrometry; mathematical modeling; mitochondria.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bacteria / chemistry
  • Barth Syndrome / metabolism
  • Cardiolipins / chemistry*
  • Cardiolipins / isolation & purification
  • Cell Line
  • Chromatography, High Pressure Liquid
  • Fatty Acids / analysis
  • Fibroblasts / chemistry
  • Fungi / chemistry
  • Humans
  • Membrane Lipids / chemistry*
  • Membrane Lipids / isolation & purification
  • Mice
  • Mitochondrial Membranes / chemistry*
  • Models, Molecular
  • Molecular Structure
  • Plants / chemistry
  • RAW 264.7 Cells
  • Tandem Mass Spectrometry
  • Vertebrates / metabolism

Substances

  • Cardiolipins
  • Fatty Acids
  • Membrane Lipids