TY - JOUR
T1 - Shotgun lipidomics of cardiolipin molecular species in lipid extracts of biological samples
AU - Han, Xianlin
AU - Yang, Kui
AU - Yang, Jingyue
AU - Cheng, Hua
AU - Gross, Richard W.
PY - 2006/4
Y1 - 2006/4
N2 - Cardiolipin is a prominent component of the mitochondrial inner membranes contributing to the regulation of multiple discrete mitochondrial functions. Here, we extend shotgun lipidomics to identify and quantitate cardiolipin molecular species directly from lipid extracts of biological samples. Three shotgun lipidomics approaches for analyses of cardiolipin molecular species were developed using either a continuous ion-transmission instrument (i.e., triple-quadrupole type) with either low or high mass resolution settings or a high mass resolution hybrid pulsed instrument [i.e., quadrupole time-of-flight (QqTOF) type]. Three chemical principles were used for the development of these approaches. These include the marked enrichment of linoleate in cardiolipin to maximize the signal-to-noise ratio, the specific neutral loss of ketenes from doubly charged cardiolipin molecular ions to yield doubly charged triacyl monolysocardiolipins, and the doubly charged character of two phosphates in each cardiolipin molecular species. Through these techniques, we identified and quantified the specific molecular species profiles of cardiolipin directly from lipid extracts of mouse heart, liver, and skeletal muscle. The accuracy (∼5%) and the low end of the linear dynamic range (10 fmol/μl) for quantitation make these approaches useful for studying alterations in cardiolipin metabolism in multiple disease states using either type of mass spectrometer.
AB - Cardiolipin is a prominent component of the mitochondrial inner membranes contributing to the regulation of multiple discrete mitochondrial functions. Here, we extend shotgun lipidomics to identify and quantitate cardiolipin molecular species directly from lipid extracts of biological samples. Three shotgun lipidomics approaches for analyses of cardiolipin molecular species were developed using either a continuous ion-transmission instrument (i.e., triple-quadrupole type) with either low or high mass resolution settings or a high mass resolution hybrid pulsed instrument [i.e., quadrupole time-of-flight (QqTOF) type]. Three chemical principles were used for the development of these approaches. These include the marked enrichment of linoleate in cardiolipin to maximize the signal-to-noise ratio, the specific neutral loss of ketenes from doubly charged cardiolipin molecular ions to yield doubly charged triacyl monolysocardiolipins, and the doubly charged character of two phosphates in each cardiolipin molecular species. Through these techniques, we identified and quantified the specific molecular species profiles of cardiolipin directly from lipid extracts of mouse heart, liver, and skeletal muscle. The accuracy (∼5%) and the low end of the linear dynamic range (10 fmol/μl) for quantitation make these approaches useful for studying alterations in cardiolipin metabolism in multiple disease states using either type of mass spectrometer.
KW - Electrospray ionization mass spectrometry
KW - Mitochondria
KW - Multidimensional mass spectrometry
UR - http://www.scopus.com/inward/record.url?scp=33645522850&partnerID=8YFLogxK
U2 - 10.1194/jlr.D500044-JLR200
DO - 10.1194/jlr.D500044-JLR200
M3 - Article
C2 - 16449763
AN - SCOPUS:33645522850
SN - 0022-2275
VL - 47
SP - 864
EP - 879
JO - Journal of lipid research
JF - Journal of lipid research
IS - 4
ER -