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Molecular Neurobiology

, Volume 42, Issue 1, pp 76–88 | Cite as

Lipids, Mitochondria and Cell Death: Implications in Neuro-oncology

  • Alison ColquhounEmail author
Article

Abstract

Polyunsaturated fatty acids (PUFAs) are known to inhibit cell proliferation of many tumour types both in vitro and in vivo. Their capacity to interfere with cell proliferation has been linked to their induction of reactive oxygen species (ROS) production in tumour tissues leading to cell death through apoptosis. However, the exact mechanisms of action of PUFAs are far from clear, particularly in brain tumours. The loss of bound hexokinase from the mitochondrial voltage-dependent anion channel has been directly related to loss of protection from apoptosis, and PUFAs can induce this loss of bound hexokinase in tumour cells. Tumour cells overexpressing Akt activity, including gliomas, are sensitised to ROS damage by the Akt protein and may be good targets for chemotherapeutic agents, which produce ROS, such as PUFAs. Cardiolipin peroxidation may be an initial event in the release of cytochrome c from the mitochondria, and enriching cardiolipin with PUFA acyl chains may lead to increased peroxidation and therefore an increase in apoptosis. A better understanding of the metabolism of fatty acids and eicosanoids in primary brain tumours such as gliomas and their influence on energy balance will be fundamental to the possible targeting of mitochondria in tumour treatment.

Keyword

Lipids Mitochondria Cell death Neuro-oncology 

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Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  1. 1.Laboratory of Tumour Cell Metabolism, Department of Cell and Developmental Biology, Biomedical Sciences InstituteUniversity of São PauloSão PauloBrazil

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