J. Cancer Mol. 3: 71-79, 2007

[Review Article]

Cancer as a “Mitochondriopathy”

Anna M Czarnecka, Antonella Marino Gammazza, Valentina Di Felice, Giovanni Zummo, and Francesco Cappello¹

Postgraduate School of Molecular Medicine, Medical University of Warsaw, Warszawa, Poland [A. M. Czarnecka]; Human Anatomy Section, Department of Experimental Medicine, University of Palermo, Palermo, Italy [A. M. Gammazza, V. D. Felice, G. Zummo, F. Cappello]

Abstract:

Mitochondria are subcellular organelles, whose well-known function is to produce ATP through the oxidative phosphorylation system.  Alterations in respiratory activity and mitochondrial DNA (mtDNA) appear to be a general feature of malignant cells.  The presence of mtDNA mutations has been reported in various cancer cells, and the abundance of mtDNA damage is consistent with the intrinsic susceptibility to constitutive oxidative stress.  Research about the functional aspects of mtDNA mutations in cancer development and therapeutic response is likely to be fruitful and to have significant clinical and prognostic impact.  Although many studies to date have been focused on the identification and characterization of altered mtDNA, it is not clear if these accumulated mutations are the cause or the consequence of the carcinogenic process.  This article provides a brief summary of our current understanding of mitochondrial pathobiology in cancer development.

Received 4/24/07; Revised 6/5/07; Accepted 6/6/07.

¹Correspondence: Dr. Francesco Cappello, Human Anatomy Section, Department of Experimental Medicine, University of Palermo, via del Vespro 129, 90127  Palermo, Italy.  Phone: 39-91-6553518. Fax: 39-91-6553518. E-mail: francapp@hotmail.com

²Abbreviations: OXPHOS, oxidative phosphorylation system; mtDNA, mitochondrial DNA; AMPK, AMP-activated kinase; SCO2, Synthesis of Cytochrome c Oxidase 2; COX, cytochrome c oxidase; D-loop, displacement loop; nDNA, nuclear DNA; ROS, reactive oxygen species; HSP, heat-shock protein; PHB, prohibitin; IM, inner mitochondrial membrane; AAA, ATP-dependent protease; mtTFA, mitochondrial transcription factor A.

Hyperlink to Full Text [PDF (6.3 MB)]