Sirt3, Mitochondrial ROS, Ageing, and Carcinogenesis

International Journal of Molecular Sciences

Seong-Hoon Park²  Ozkan Ozden²  Haiyan Jiang²  Yong I. Cha²  J. Daniel Pennington²  Nukhet Aykin-Burns¹  Douglas R. Spitz¹  David Gius² 

[1] Free Radical and Radiation Biology Program, Department of Radiation Oncology, Holden Comprehensive Cancer Center, The University of Iowa, Iowa City, IA 52242, USA; E-Mails:;Department of Cancer Biology, Pediatrics, and Radiation Oncology, Vanderbilt University Medical Center, Nashville, TN 37232, USA; E-Mails:

关键词: Sirt3;    mitochondria;    acetylation;    acetylome;    cancer;    MnSOD;    carcinogenesis;    receptor positive breast cancer;   

DOI  :  10.3390/ijms12096226

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2011 by the authors; licensee MDPI, Basel, Switzerland.