Mitochondrial proteome: Altered cytochrome c oxidase subunit levels in prostate cancer

Paul C. Herrmann*, John W. Gillespie, Lu Charboneau, Verena E. Bichsel, Cloud P. Paweletz, Valerie S. Calvert, Elise C. Kohn, Michael R. Emmert-Buck, Lance A. Liotta, Emanuel F. Petricoin

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

135 Scopus citations

Abstract

Laser capture microdissection was combined with reverse phase protein lysate arrays to quantitatively analyze the ratios of mitochondrial encoded cytochrome c oxidase subunits to nuclear encoded cytochrome c oxidase subunits, and to correlate the ratios with malignant progression in human prostate tissue specimens. Cytochrome c oxidase subunits I-III comprise the catalytic core of the enzyme and are all synthesized from mitochondrial DNA. The remaining subunits (IV-VIII) are synthesized from cellular nuclear DNA. A significant (P < 0.001, 30/30 prostate cases) shift in the relative concentrations of nuclear encoded cytochrome c oxidase subunits IV, Vb, and VIc compared to mitochondrial encoded cytochrome c oxidase subunits I and II was noted during the progression of prostate cancer from normal epithelium through premalignant lesions to invasive carcinoma. Significantly, this shift was discovered to begin even in the premalignant stage. Reverse phase protein lysate array-based observations were corroborated with immunohistochemistry and extended to a few human carcinomas in addition to prostate. This analysis points to a role for nuclear DNA encoded mitochondrial proteins in carcinogenesis; underscoring their potential as targets for therapy while highlighting the need for full characterization of the mitochondrial proteome.

Original languageEnglish
Pages (from-to)1801-1810
Number of pages10
JournalProteomics
Volume3
Issue number9
DOIs
StatePublished - 1 Sep 2003
Externally publishedYes

Keywords

  • Cancer
  • Cytochrome c oxidase
  • Mitochondrial proteome
  • Oxidative phosphorylation
  • Prostate

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