SIRT3 is a Mitochondrial Localized Tumor Suppressor Required for Maintenance of Mitochondrial Integrity and Metabolism During Stress
By Hyunseok Kim, K. Patel, Kristi Muldoon-Jacobs, K. Bisht, N. Aykin-Burns, J. Pennington, R. van der Meer, P. Nguyen, J. Savage, K. Owens and 8 more. Cancer Cell, 2010
853 citations recorded by the source corpus.
SUMMARY 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, mitochondrial localized tumor suppressor.
Subfields: Epidemiology, Geriatrics and Gerontology, Molecular Biology
View Paper: https://www.semanticscholar.org/paper/83de78ee37c13a9455d6704b72fdd1112ab24ae9
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Citations in the corpus
- Calorie restriction reduces oxidative stress by SIRT3-mediated SOD2 activation. (2010, background): “SOD2 was identified in mass spectrometry-based screens for acetylated peptides (Choudhary et al., 2009; Kim et al., 2006, 2010; Schwer et al., 2009).”
- SIRTUIN 1 AND SIRTUIN 3: PHYSIOLOGICAL MODULATORS OF METABOLISM (2012, background): “Another important effect of the global deficiency of SIRT3 was that these mice had increased stress-induced superoxide levels and genomic instability, leading to a tumor-permissive phenotype (171).”
- SIRT3 Deficiency and Mitochondrial Protein Hyperacetylation Accelerate the Development of the Metabolic Syndrome (2011, neutral): “, 2008), and increased reactive oxygen species (Kim et al., 2010; Qiu et al., 2010; Someya et al., 2010; Tao et al., 2010).”
- Mitochondrial Dysfunction Induces Senescence with a Distinct Secretory Phenotype (2015, background): “Our finding that loss of SIRT3 loss drives senescence appears to contradict a report in which cells from SIRT3 knockout mice were highly susceptible to oncogenic transformation; however, this susceptibility depended on the elevated ROS characteristic of sirt3 / cells (Kim et al., 2010).”
- SIRT3 opposes reprogramming of cancer cell metabolism through HIF1α destabilization (2011, background): “Because breast cancers exhibited exceptionally high frequency of SIRT3 deletions compared to other tumor types (Figure 5D) (Kim et al., 2010), we further examined SIRT3 in human breast cancers.”
- Mitochondria-Ros Crosstalk in the Control of Cell Death and Aging (2011, background): “SIRT3 is required for the maintenance of mitochondrial integrity and metabolism during stress [190].”
- Influence of Metabolism on Epigenetics and Disease (2013, positive): “Recent studies have provided evidence that the genes encoding SIRT3 and SIRT6 are tumor suppressors (Kim et al., 2010; Sebastián et al., 2012).”
- Sirt3-Mediated Deacetylation of Evolutionarily Conserved Lysine 122 Regulates MnSOD Activity in Response to Stress (2010, methodology): “(C) Mitochondrial superoxide levels were determined in wild-type and Sirt3 / MEFs using MitoSOX oxidation at culture passage number three, as previously described (Kim et al., 2010).”