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

• Type of Material: Article
• Authors: Rebecca Arnold, Emory University; Qian Sun, Emory University; Carrie Q. Sun, Emory University; Jendai C. Richards, Emory University; Sean O'Hearn, University of California Irvine; Adeboye O. Osunkoya, Emory University; Douglas C. Wallace, University of California Irvine; John A Petros, Emory University
• Language: English
• Date: 2012-08-09
• Publisher: Hindawi Publishing Corporation
• Publication Version: Final Published Version
• Copyright Statement: © 2013 Rebecca S. Arnold et al.
• License: Creative Commons Attribution 3.0 Unported
• Final Published Version (URL): http://www.hindawi.com/journals/bmri/2013/239257/
• Title of Journal or Parent Work: BioMed Research International
• ISSN: 2314-6133
• Volume: 2013
• Issue: 2013
• Start Page: 1
• End Page: 10
• Grant/Funding Information: This work is supported by NIH Grant nos. CA98912 (Petros), CA96994 (Petros), and NS21328 (Wallace). It is also supported by a VA MERIT award (Petros). The authors wish to thank Mr. Larry Williams (The Breckenridge Group) for his personal support of this research and the Evans County Cares Foundation. In addition, cytochrome oxidase activity assays performed by Leslie Costello, Ph.D. (University of Maryland). Technical help was also provided by Amanda Parrish Ph.D. and Carina Fenandez-Golarz M.D.
• Research Categories: Health Sciences, Oncology

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.