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, Hyun Seok Kim*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

70 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)6226-6239
Number of pages14
JournalInternational journal of molecular sciences
Volume12
Issue number9
DOIs
StatePublished - Sep 2011

Keywords

  • Acetylation
  • Acetylome
  • Cancer
  • Carcinogenesis
  • Mitochondria
  • MnSOD
  • Receptor positive breast cancer
  • Sirt3

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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