SIRT3 is a mitochondrial tumor suppressor: A scientific tale that connects aberrant cellular ROS, the Warburg effect, and carcinogenesis

Marcia C. Haigis, Chu Xia Deng, Lydia W.S. Finley, Hyun Seok Kim, David Gius

Research output: Contribution to journalReview articlepeer-review

144 Scopus citations

Abstract

Tumors exhibit metabolic reprogramming characterized by increased cellular reactive oxygen species (ROS) and the preferential use of glucose, which is known as the Warburg effect. However, the mechanisms by which these processes are linked remain largely elusive. Murine tumors lacking Sirt3 exhibit abnormally high levels of ROS that directly induce genomic instability and increase hypoxia-inducible factor 1α(HIF-1α) protein levels. The subsequent transcription of HIFα-dependent target genes results in cellular metabolic reprogramming and increased cellular glucose consumption. In addition, agents that scavenge ROS or reverse the Warburg effect prevent the transformation and malignant phenotype observed in cells lacking Sirt3. Thus, mice lacking Sirt3 provide a model that mechanistically connects aberrant ROS, the Warburg effect, and carcinogenesis.

Original languageEnglish
Pages (from-to)2468-2472
Number of pages5
JournalCancer Research
Volume72
Issue number10
DOIs
StatePublished - 15 May 2012

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