Mechanisms associated with mitochondrial-generated reactive oxygen species in cancer

The mitochondria are unique cellular organelles that contain their own genome and, in conjunction with the nucleus, are able to transcribe and translate genes encoding components of the electron transport chain (ETC). To do so, the mitochondria must communicate with the nucleus via the production of...

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Bibliographic Details
Published in:Canadian journal of physiology and pharmacology 2010-03, Vol.88 (3), p.204-219
Main Authors: VERSCHOOR, Meghan L, WILSON, Leigh A, SINGH, Gurmit
Format: Article
Language:English
Subjects:
Amino acids
Animals
Biological and medical sciences
Cancer
Colorectal cancer
DNA binding proteins
Fundamental and applied biological sciences. Psychology
Gene expression
Genetic aspects
Humans
Medical treatment
Mitochondria
Mitochondria - genetics
Mitochondria - metabolism
Mutation - genetics
Neoplasms - genetics
Neoplasms - metabolism
Reactive Oxygen Species - metabolism
Signal Transduction - physiology
Studies
Transcription Factors - genetics
Transcription Factors - metabolism
Tumor proteins
Vertebrates: anatomy and physiology, studies on body, several organs or systems
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Summary:The mitochondria are unique cellular organelles that contain their own genome and, in conjunction with the nucleus, are able to transcribe and translate genes encoding components of the electron transport chain (ETC). To do so, the mitochondria must communicate with the nucleus via the production of reactive oxygen species (ROS) such as hydrogen peroxide (H2O2), which are produced as a byproduct of aerobic respiration within the mitochondria. Mitochondrial signaling is proposed to be altered in cancer cells, where the mitochondria are frequently found to harbor mutations within their genome and display altered functional characteristics leading to increased glycolysis. As signaling molecules, ROS oxidize and inhibit MAPK phosphatases resulting in enhanced proliferation and survival, an effect particularly advantageous to cancer cells. In terms of transcriptional regulation, ROS affect the phosphorylation, activation, oxidation, and DNA binding of transcription factors such as AP-1, NF-kappaB, p53, and HIF-1alpha, leading to changes in target gene expression. Increased ROS production by defective cancer cell mitochondria also results in the upregulation of the transcription factor Ets-1, a factor that has been increasingly associated with aggressive cancers.
ISSN:0008-4212
1205-7541
DOI:10.1139/Y09-135