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Sirt3, Mitochondrial ROS, Ageing, and Carcinogenesis
Journal article   Open access   Peer reviewed

Sirt3, Mitochondrial ROS, Ageing, and Carcinogenesis

Seong-Hoon Park, Ozkan Ozden, Haiyan Jiang, Yong I Cha, J. Daniel Pennington, Nukhet Aykin-Burns, Douglas R Spitz, David Gius and Hyun-Seok Kim
International journal of molecular sciences, Vol.12(9), pp.6226-6239
09/2011
DOI: 10.3390/ijms12096226
PMCID: PMC3189778
PMID: 22016654
url
https://doi.org/10.3390/ijms12096226View
Published (Version of record) Open Access

Abstract

One fundamental observation in cancer etiology is that the rate of malignancies in any mammalian population increases exponentially as a function of age, suggesting a mechanistic link between the cellular processes governing longevity and carcinogenesis. In addition, it is well established that aberrations in mitochondrial metabolism, as measured by increased reactive oxygen species (ROS), are observed in both aging and cancer. In this regard, genes that impact upon longevity have recently been characterized in S. cerevisiae and C. elegans , and the human homologs include the Sirtuin family of protein deacetylases. Interestingly, three of the seven sirtuin proteins are localized into the mitochondria suggesting a connection between the mitochondrial sirtuins, the free radical theory of aging, and carcinogenesis. Based on these results it has been hypothesized that Sirt3 functions as a mitochondrial fidelity protein whose function governs both aging and carcinogenesis by modulating ROS metabolism. Sirt3 has also now been identified as a genomically expressed, mitochondrial localized tumor suppressor and this review will outline potential relationships between mitochondrial ROS/superoxide levels, aging, and cell phenotypes permissive for estrogen and progesterone receptor positive breast carcinogenesis.
acetylation carcinogenesis mitochondria acetylome MnSOD Sirt3 cancer Review receptor positive breast cancer

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