title: An inherited heteroplasmic mutation in mitochondrial gene COI in a patient with prostate cancer alters reactive oxygen, reactive nitrogen and proliferation.
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.
authors.affiliation: Department of Urology, School of Medicine, Emory University, 1365 Clifton Rd. Building B, Atlanta, GA 30322, USA.
authors.forename: Rebecca S
authors.initials: RS
authors.lastname: Arnold
authors.forename: Qian
authors.initials: Q
authors.lastname: Sun
authors.forename: Carrie Q
authors.initials: CQ
authors.lastname: Sun
authors.forename: Jendai C
authors.initials: JC
authors.lastname: Richards
authors.forename: Sean
authors.initials: S
authors.lastname: O'Hearn
authors.forename: Adeboye O
authors.initials: AO
authors.lastname: Osunkoya
authors.forename: Douglas C
authors.initials: DC
authors.lastname: Wallace
authors.forename: John A
authors.initials: JA
authors.lastname: Petros
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D003576:Electron Transport Complex IV / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D050259:Genes, Mitochondrial; D006801:Humans; D008297:Male; D051379:Mice; D008875:Middle Aged; D008928:Mitochondria / Q000201:enzymology*; D009154:Mutation; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism*; D026361:Reactive Nitrogen Species / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species; D003576:Electron Transport Complex IV