文档介绍：Cardiolipin and electron transport chain abnormalities in
mouse brain tumor mitochondria: lipidomic evidence
supporting the Warburg theory of cancer
††
Michael A. Kiebish,* Xianlin Han, Hua Cheng, Jeffrey H. Chuang,* and Thomas N. Seyfried1,*
†
Department of Biology,* Boston College, Chestnut Hill, MA; and Department of Internal Medicine,
Washington University School of Medicine, St. Louis, MO
Abstract Otto Warburg first proposed that cancer origi- that was followed in time by a gradual dependence on fer-
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nated from irreversible injury to mitochondrial respiration, mentation (glycolytic) energy pensate for the en-
but the structural basis for this injury has remained elusive. ergy lost from respiration. Cell viability requires a constant
Cardiolipin (CL) is plex phospholipid found almost delta G′ of ATP hydrolysis of approximately 257 kJ/mol
exclusively in the inner mitochondrial membrane and is in-
(3, 4). Most normal mammalian cells achieve this level
timately involved in maintaining mitochondrial functionality
and membrane integrity. Abnormalities in CL can impair of useable energy through respiration, whereas tumor
mitochondrial function and bioenergetics. We used shotgun cells achieve this level through bination of respira-
lipidomics to analyze CL content position in highly tion and glycolysis (2, 5). Indeed, elevated glycolysis is
purified brain mitochondria from the C57BL/6J (B6) and the metabolic hallmark of nearly all tumors, including
VM/Dk (VM) inbred strains and from subcutaneously grown brain tumors, and is the basis for tumor imaging using at Univ of Ottawa - OCUL on December 1, 2008
brain tumors derived from these strains to include an astro- labeled glucose analogs (5–8). Much controversy has sur-
cytoma and ependymoblastoma (B6 tumors), a stem cell tumor, rounded the Warburg theory, however, largely over issues
and two microgliomas (VM tumors). Major abnormalities in regarding the Pasture effect and