Brain mitochondrial lipid abnormalities in mice susceptible to spontaneous gliomas

Michael A. Kiebish, Xianlin Han, Hua Cheng, Jeffrey H. Chuang, Thomas N. Seyfried

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Alterations in mitochondrial function have long been considered a hallmark of cancer. We compared the lipidome and electron transport chain activities of non-synaptic brain mitochondria in two inbred mouse strains, the C57BL/6J (B6) and the VM/Dk (VM). The VM strain is unique in expressing a high incidence of spontaneous brain tumors (1.5%) that are mostly gliomas. The incidence of gliomas is about 210-fold greater in VM mice than in B6 mice. Using shotgun lipidomics, we found that the mitochondrial content of ethanolamine glycerophospholipid, phosphatidylserine, and ceramide was higher, whereas the content of total choline glycerophospholipid was lower in the VM mice than in B6 mice. Total cardiolipin content was similar in the VM and the B6 mice, but the distribution of cardiolipin molecular species differed markedly between the strains. B6 non-synaptic mitochondria contained 95 molecular species of cardiolipin that were symmetrically distributed over 7 major groups based on mass charge. In contrast, VM non-synaptic mitochondria contained only 42 molecular species that were distributed asymmetrically. The activities of Complex I, I/III, and II/III enzymes were lower, whereas the activity of complex IV was higher in the mitochondria of VM mice than in B6 mice. The high glioma incidence and alterations in electron transport chain activities in VM mice compared to B6 mice could be related to the unusual composition of mitochondrial lipids in the VM mouse brain.

Original languageEnglish (US)
Pages (from-to)951-959
Number of pages9
JournalLipids
Volume43
Issue number10
DOIs
StatePublished - Oct 1 2008
Externally publishedYes

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Mitochondria
Glioma
Cardiolipins
Brain
Lipids
Glycerophospholipids
Ethanolamine
Ceramides
Phosphatidylserines
Phosphatidylcholines
Tumors
Electron Transport
Incidence
Enzymes
Chemical analysis
Inbred Strains Mice
Firearms
Brain Neoplasms

ASJC Scopus subject areas

  • Biochemistry
  • Organic Chemistry
  • Cell Biology

Cite this

Brain mitochondrial lipid abnormalities in mice susceptible to spontaneous gliomas. / Kiebish, Michael A.; Han, Xianlin; Cheng, Hua; Chuang, Jeffrey H.; Seyfried, Thomas N.

In: Lipids, Vol. 43, No. 10, 01.10.2008, p. 951-959.

Research output: Contribution to journalArticle

Kiebish, Michael A. ; Han, Xianlin ; Cheng, Hua ; Chuang, Jeffrey H. ; Seyfried, Thomas N. / Brain mitochondrial lipid abnormalities in mice susceptible to spontaneous gliomas. In: Lipids. 2008 ; Vol. 43, No. 10. pp. 951-959.
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