Mitochondria remodeling in cancer

Kenneth J. Dornfeld, Andrew J Skildum

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

Cancer cells are characterized by altered metabolism and uncontrolled proliferation. It is not surprising that mitochondria, which serve important roles in fuel oxidation (catabolism) and synthesizing biosynthetic precursors (anabolism), are altered in cancer cells. Although most cancer cells have increased uptake of glucose and upregulation of glycolysis, mitochondria remain essential for carcinogenesis. However, cancer cell mitochondria have significant differences that distinguish them from those of normal cells. Mitochondria of cancer cells often have decreased electron transport capacity, depressed ATP generation, and increased production of reactive oxygen species. These alterations in metabolism promote nutrient uptake, support increased proliferation and afford resistance to apoptotic cell death. The specific metabolic processes in cancer provide opportunities to selectively target them pharmacologically to improve outcomes for cancer patients. In cancer diagnosis, tumor metabolism can be inferred from gene expression patterns and mutations, rates of nutrient uptake, and from direct measurement of metabolites. In treatment, these processes can be specifically targeted. Alterations in metabolism, mitochondrial DNA, the electron transport chain, and tricarboxylic acid cycle enzymes in cancer are described. The exploitation of these differences for diagnosis and treatment are discussed, with a review of select agents currently in clinical use or under active investigation.

Original languageEnglish (US)
Title of host publicationMitochondrial Biology and Experimental Therapeutics
PublisherSpringer International Publishing
Pages153-191
Number of pages39
ISBN (Electronic)9783319733449
ISBN (Print)9783319733432
DOIs
StatePublished - Mar 21 2018

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Keywords

  • Anabolism
  • Cancer
  • Chemotherapy
  • Glycolysis
  • Tricarboxylic acid cycle
  • Warburg

Cite this

Dornfeld, K. J., & Skildum, A. J. (2018). Mitochondria remodeling in cancer. In Mitochondrial Biology and Experimental Therapeutics (pp. 153-191). Springer International Publishing. https://doi.org/10.1007/978-3-319-73344-9_9