Tumour suppressor SIRT3 deacetylates and activates manganese superoxide dismutase to scavenge ROS

Abstract

Tumour suppressor SIRT3 deacetylates and activates manganese superoxide dismutase to scavenge ROSMitochondria manganese superoxide dismutase (SOD2) is a major antioxidant enzyme associated with several diseases. This study shows that SOD2 is inhibited by acetylation and activated by SIRT3-mediated deacetylation in response to reactive oxygen species (ROS).

The Protein Deacetylase SIRT3 Prevents Oxidative Stress-induced Keratinocyte Differentiation

“…Keratinocytes-SIRT3 acts through several targets to both reduce superoxide production and enhance the oxidative stress response and detoxification mechanisms (8,(11)(12)(13)(14)(15)(16)(17). Consistent with the repression of mitochondrial oxidative stress by SIRT3, mitochondrial superoxide levels decreased in SIRT3-overexpressing keratinocytes (Fig.…”

“…Decreased availability of the sirtuin co-substrate NAD ϩ may lead to decreased SIRT3 activity in keratinocytes during differentiation. Given the well established role of SIRT3 as a regulator of mitochondrial oxidative stress (8,(11)(12)(13)(14)(15)(16)(17)(18), mitochondrial superoxide levels increased in both primary and immortalized keratinocytes with differentiation. We identified SIRT3 as a key regulator of this phenotype; constitutive SIRT3 deficiency resulted in increased mitochondrial superoxide levels, whereas constitutive SIRT3 expression reduced mitochondrial ROS.…”

“…It binds and deacetylates several mitochondrial proteins that promote mitochondrial oxidative metabolism, such as electron transport chain subunits and fatty acid oxidation enzymes (9,10). SIRT3 also dampens mitochondrial oxidative stress via deacetylation and subsequent activation of SOD2 and isocitrate dehydrogenase (8,(11)(12)(13)(14)(15)(16)(17)(18).…”

Insulin and IGF-1 improve mitochondrial function in a PI-3K/Akt-dependent manner and reduce mitochondrial generation of reactive oxygen species in Huntington’s disease knock-in striatal cells

“…3B). Since acetylation of SOD2 at Lys68 was reported to decrease its activity [50], we measured the acetylation levels of SOD2 in striatal cells. In agreement with increased SOD2 activity, we detected a decrease in Ac-SOD2/SOD2 ratio in mutant cells (Fig.…”

Do Sirtuins Promote Mammalian Longevity?: A Critical Review on Its Relevance to the Longevity Effect Induced by Calorie Restriction

“…SIRT3 was downregulated in response to a high-fat diet, leadi n g t o d e v e l o p m e n t o f m e t a b o l i c s y n d r o m e through mitochondrial protein hyperacetylation (Green and Hirschey, 2013). SIRT3 also appears to be an antioxidant protein, as SIRT3 reduced reactive oxygen species (ROS) through post-translational regulation of superoxide dismutase 2 (SOD2) via deactylation in response to oxidative stress (Chen et al, 2011). Furthermore, SIRT3 is involved in fatty acid oxidation in the liver (Giralt and Villarroya, 2012).…”