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Current Genomics

Editor-in-Chief

ISSN (Print): 1389-2029
ISSN (Online): 1875-5488

Emerging Concepts in the Analysis of Mitochondrial Genome Instability

Author(s): Raphael Saffroy, Franck Chiappini, Brigitte Debuire and Antoinette Lemoine

Volume 5, Issue 4, 2004

Page: [309 - 325] Pages: 17

DOI: 10.2174/1389202043349228

Price: $65

Abstract

Nuclear genome instability is known to play an important role in the origin of some human cancers. However, eukaryotic cells also have cytoplasmic genomes that are compartimentalised in the mitochondria. Mitochondria (mt) are essential for the regulation of several aspects of cell biology such as energy production, maintenance of redox status, molecular metabolism, calcium signalling and apoptosis. Oxidative stress causes significant mtDNA damage, which is thought to increase the risk of a growing number of degenerative diseases. MtDNA is highly suscepectable to mutations and contains fewer repair mechanisms than nuclear DNA, thus it may contribute to aging and be associated with the initial stages of carcinogenesis. Mitochondrial dysfunction might explain the dose-limiting toxicity of various therapeutic agents such as the nucleoside analogues used to combat HIV and hepatitis B viruses. The mitochondrial genome may represent a potential target for the development of cancer therapy. The role of mt-genomes in human diseases and in particular, in malignancy is still not fully understood. In this review, we focus on mitochondrial genome aberrations such as point mutations, instability of mono- or dinucleotide repeat, long deletions and change of the mtDNA copy number. The potential role played by mitochondria and mtDNA aberrations in malignancy, and the potential clinical use of the mtDNA markers are discussed.

Keywords: Mitochondrial Genome, dinucleotide, malignancy, mtDNA


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