SIRT3 Is a Mitochondria-Localized Tumor Suppressor Required for Maintenance of Mitochondrial Integrity and Metabolism during Stress

Academic Article

Abstract

  • The sirtuin gene family (SIRT) is hypothesized to regulate the aging process and play a role in cellular repair. This work demonstrates that SIRT3-/- mouse embryonic fibroblasts (MEFs) exhibit abnormal mitochondrial physiology as well as increases in stress-induced superoxide levels and genomic instability. Expression of a single oncogene (Myc or Ras) in SIRT3-/- MEFs results in in vitro transformation and altered intracellular metabolism. Superoxide dismutase prevents transformation by a single oncogene in SIRT3-/- MEFs and reverses the tumor-permissive phenotype as well as stress-induced genomic instability. In addition, SIRT3-/- mice develop ER/PR-positive mammary tumors. Finally, human breast and other human cancer specimens exhibit reduced SIRT3 levels. These results identify SIRT3 as a genomically expressed, mitochondria-localized tumor suppressor. © 2010 Elsevier Inc. All rights reserved.
  • Digital Object Identifier (doi)

    Author List

  • Kim HS; Patel K; Muldoon-Jacobs K; Bisht KS; Aykin-Burns N; Pennington JD; van der Meer R; Nguyen P; Savage J; Owens KM
  • Start Page

  • 41
  • End Page

  • 52
  • Volume

  • 17
  • Issue

  • 1