Lipid analogues as potential drugs for the regulation of mitochondrial cell death

Michael Murray, Herryawan Ryadi Eziwar Dyari, Sarah E. Allison, Tristan Rawling

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

The mitochondrion plays an important role in the production of energy as ATP, the regulation of cell viability and apoptosis, and the biosynthesis of major structural and regulatory molecules, such as lipids. During ATP production, reactive oxygen species are generated that alter the intracellular redox state and activate apoptosis. Mitochondrial dysfunction is a well-recognized component of the pathogenesis of diseases such as cancer. Understanding mitochondrial function, and how this is dysregulated in disease, offers the opportunity for the development of drug molecules to specifically target such defects. Altered energy metabolism in cancer, in which ATP production occurs largely by glycolysis, rather than by oxidative phosphorylation, is attributable in part to the up-regulation of cell survival signalling cascades. These pathways also regulate the balance between pro- and anti-apoptotic factors that may determine the rate of cell death and proliferation. A number of anti-cancer drugs have been developed that target these factors and one of the most promising groups of agents in this regard are the lipid-based molecules that act directly or indirectly at the mitochondrion. These molecules have emerged in part from an understanding of the mitochondrial actions of naturally occurring fatty acids. Some of these agents have already entered clinical trials because they specifically target known mitochondrial defects in the cancer cell.

Original languageEnglish
Pages (from-to)2051-2066
Number of pages16
JournalBritish Journal of Pharmacology
Volume171
Issue number8
DOIs
Publication statusPublished - 2014
Externally publishedYes

Fingerprint

Drug and Narcotic Control
Cell Death
Lipids
Adenosine Triphosphate
Neoplasms
Cell Survival
Mitochondria
Apoptosis
Oxidative Phosphorylation
Glycolysis
Pharmaceutical Preparations
Energy Metabolism
Oxidation-Reduction
Reactive Oxygen Species
Up-Regulation
Fatty Acids
Cell Proliferation
Clinical Trials

Keywords

  • cancer cell
  • ether phospholipids
  • fatty acid biotransformation
  • free fatty acids
  • intrinsic pathway of apoptosis
  • mitochondrial ATP production
  • N-acylethanolamines
  • polyunsaturated fatty acid epoxides
  • reactive oxygen species

ASJC Scopus subject areas

  • Pharmacology
  • Medicine(all)

Cite this

Lipid analogues as potential drugs for the regulation of mitochondrial cell death. / Murray, Michael; Eziwar Dyari, Herryawan Ryadi; Allison, Sarah E.; Rawling, Tristan.

In: British Journal of Pharmacology, Vol. 171, No. 8, 2014, p. 2051-2066.

Research output: Contribution to journalArticle

Murray, Michael ; Eziwar Dyari, Herryawan Ryadi ; Allison, Sarah E. ; Rawling, Tristan. / Lipid analogues as potential drugs for the regulation of mitochondrial cell death. In: British Journal of Pharmacology. 2014 ; Vol. 171, No. 8. pp. 2051-2066.
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