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BioMed Research International
Volume 2013 (2013), Article ID 239257, 10 pages
http://dx.doi.org/10.1155/2013/239257
Research Article

An Inherited Heteroplasmic Mutation in Mitochondrial Gene COI in a Patient with Prostate Cancer Alters Reactive Oxygen, Reactive Nitrogen and Proliferation

1Department of Urology, School of Medicine, Emory University, 1365 Clifton Rd. Building B, Atlanta, GA 30322, USA
2Winship Cancer Institute, Emory University, Atlanta, GA 30322, USA
3Center for Molecular and Mitochondrial Medicine and Genetics (MAMMAG), University of California Irvine, Irvine, CA 92697, USA
4Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA 30322, USA
5Department of Urology, The Atlanta VA Medical Center, Decatur, GA 30033, USA
6Center for Mitochondrial and Epigenomic Medicine, Children's Hospital of Philadelphia and Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
7Department of Pathology, University of Pennsylvania, Philadelphia, PA 19104, USA

Received 6 June 2012; Revised 8 August 2012; Accepted 9 August 2012

Academic Editor: Gurmit Singh

Copyright © 2013 Rebecca S. Arnold et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Mitochondrial DNA (mtDNA) mutations have been found in many cancers but the physiological derangements caused by such mutations have remained elusive. Prostate cancer is associated with both inherited and somatic mutations in the cytochrome c oxidase (COI) gene. We present a prostate cancer patient-derived rare heteroplasmic mutation of this gene, part of mitochondrial respiratory complex IV. Functional studies indicate that this mutation leads to the simultaneous decrease in cytochrome oxidation, increase in reactive oxygen, and increased reactive nitrogen. These data suggest that mitochondrial DNA mutations resulting in increased reactive oxygen and reactive nitrogen generation may be involved in prostate cancer biology.