Sirt3 knockout: Sirt3 is a mitochondrial-localized tumor suppressor that maintains mitochondrial integrity and metabolism during stress.
Sirt3 is a mitochondrial protein that is a member of the Sirtuin family of NAD-dependent protein deacetylases. Sirt3(-/-) mice are phenotypically normal, but exhibit many proteins whose acetylation is increased. They generate more reactive oxygen species and are more susceptible to mammary tumors than normal mice. Sirt3 is inactivated in a large percentage of human breast and ovarian cancers, suggesting that Sirt3 may be a mitochondria-localized tumor suppressor by maintaining mitochondrial integrity and efficient oxidative metabolism.