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Review
. 2016 Feb 19;5(1):7.
doi: 10.3390/antiox5010007.

Mitochondrial Dysfunction in Cancer and Neurodegenerative Diseases: Spotlight on Fatty Acid Oxidation and Lipoperoxidation Products

Giuseppina Barrera  1 , Fabrizio Gentile  2 , Stefania Pizzimenti  3 , Rosa Angela Canuto  4 , Martina Daga  5 , Alessia Arcaro  6 , Giovanni Paolo Cetrangolo  7 , Alessio Lepore  8 , Carlo Ferretti  9 , Chiara Dianzani  10 , Giuliana Muzio  11
Affiliations
Review

Mitochondrial Dysfunction in Cancer and Neurodegenerative Diseases: Spotlight on Fatty Acid Oxidation and Lipoperoxidation Products

Giuseppina Barrera et al. Antioxidants (Basel). .

Abstract

In several human diseases, such as cancer and neurodegenerative diseases, the levels of reactive oxygen species (ROS), produced mainly by mitochondrial oxidative phosphorylation, is increased. In cancer cells, the increase of ROS production has been associated with mtDNA mutations that, in turn, seem to be functional in the alterations of the bioenergetics and the biosynthetic state of cancer cells. Moreover, ROS overproduction can enhance the peroxidation of fatty acids in mitochondrial membranes. In particular, the peroxidation of mitochondrial phospholipid cardiolipin leads to the formation of reactive aldehydes, such as 4-hydroxynonenal (HNE) and malondialdehyde (MDA), which are able to react with proteins and DNA. Covalent modifications of mitochondrial proteins by the products of lipid peroxidation (LPO) in the course of oxidative cell stress are involved in the mitochondrial dysfunctions observed in cancer and neurodegenerative diseases. Such modifications appear to affect negatively mitochondrial integrity and function, in particular energy metabolism, adenosine triphosphate (ATP) production, antioxidant defenses and stress responses. In neurodegenerative diseases, indirect confirmation for the pathogenetic relevance of LPO-dependent modifications of mitochondrial proteins comes from the disease phenotypes associated with their genetic alterations.

Keywords: cancer; fatty acid oxidation; lipoperoxidation products; mitochondria; neurodegenerative diseases.

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Figure 1
Effects of mitochondrial ROS in cancer cells.
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