%0 Journal Article
%T The Importance of Mitochondrial DNA in Aging and Cancer
%A Claus Desler
%A Maiken Lise Marcker
%A Keshav K. Singh
%A Lene Juel Rasmussen
%J Journal of Aging Research
%D 2011
%I Hindawi Publishing Corporation
%R 10.4061/2011/407536
%X Mitochondrial dysfunction has been implicated in premature aging, age-related diseases, and tumor initiation and progression. Alterations of the mitochondrial genome accumulate both in aging tissue and tumors. This paper describes our contemporary view of mechanisms by which alterations of the mitochondrial genome contributes to the development of age- and tumor-related pathological conditions. The mechanisms described encompass altered production of mitochondrial ROS, altered regulation of the nuclear epigenome, affected initiation of apoptosis, and a limiting effect on the production of ribonucleotides and deoxyribonucleotides. 1. Introduction Mitochondria are semiautonomous organelles present in almost all eukaryotic cells in quantities ranging from a single copy to several thousands per cell. Important mitochondrial functions include ATP production by oxidative phosphorylation, ¦Â-oxidation of fatty acids, and metabolism of amino acids and lipids. Furthermore, mitochondria have a prominent role in apoptosis initiation. The circular mitochondrial DNA (mtDNA) is more susceptible to DNA damages in comparison to nuclear DNA (nDNA). Importantly, mtDNA molecules are not protected by histones, they are supported with only rudimentary DNA repair and are localized in close proximity to the electron transport chain (ETC), which continuously generates oxidizing products known as reactive oxygen species (ROS). Thus, the mutation rate of mtDNA has been reported to be up to 15-fold higher than observed for nDNA in response to DNA damaging agents [1]. Mitochondrial dysfunction and especially dysfunctions caused by mutations of the mtDNA have been implicated with a wide range of age-related pathologies, including cancers, neurodegenerative diseases and, in general, processes that regulate cellular and organismal aging. The mitochondrial genome encodes peptides essential for the function of the ETC and production of ATP by oxidative phosphorylation. Electrons are primarily donated to the ETC from the Krebs cycle, but other sources also contribute. The human enzyme dihydroorotate dehydrogenase (DHODHase), an integral part of the de novo synthesis of pyrimidines, is coupled to the ETC [2, 3]. The activity of the enzyme is dependent on its ability to transfer electrons to the ETC. ATP is the primary product of oxidative phosphorylation, but certain molecules of ROS are also generated continuously [4, 5]. At subtoxic concentrations, ROS has been demonstrated to function as second messenger molecules proposed to report oxygen availability for oxidative phosphorylation and
%U http://www.hindawi.com/journals/jar/2011/407536/