BACKGROUND Sirtuins (SIRT1-7) are a family of NAD-dependent deacetylases and/or ADP-ribosyltransferases that are involved in metabolism, stress responses and longevity. SIRT3 is localized to mitochondria, where it deacetylates and activates a number of enzymes involved in fuel oxidation and energy production. METHODOLOGY/PRINCIPAL FINDINGS In this study, we performed a proteomic screen to ide...

Acute kidney injury (AKI) is a public health concern with an annual mortality rate that exceeds those of breast and prostate cancer, heart failure, and diabetes combined. Oxidative stress and mitochondrial damage are drivers of AKI-associated pathology; however, the pathways that mediate these events are poorly defined. Here, using a murine cisplatin-induced AKI model, we determined that both o...

SIRT3 is a major regulator of mitochondrial acetylome. Here we show that neuroprotective in Huntington's disease (HD), motor neurodegenerative disorder caused by an abnormal expansion polyglutamines the huntingtin protein (HTT). Protein and enzymatic analysis revealed increased signature several HD models, including human brain, which regulated oxidative species. While loss further aggravated p...

BACKGROUND Mammalian sirtuins are homologs to the yeast silent information regulator 2 (Sir2), which is an NAD-dependent deacetylase. Sirtuins are comprised of 7 proteins, and each has different target proteins. Sirtuin 1 (SIRT1) plays important roles in maintaining metabolic functions and immune responses, and SIRT3 protects cells from oxidative stress-induced cell death. Both SIRT1 and SIRT3 ...

Sirtuin1 (Sirt1) and Sirtuin3 (Sirt3) are two well-characterized members of the silent information regulator 2 (Sir2) family of proteins. Both Sirt1 and Sirt3 have been shown to play vital roles in resistance to cellular stress, but the interaction between these two sirtuins has not been fully determined. In this study, we investigated the role of Sirt1-Sirt3 axis in blood-brain barrier (BBB) p...

Constitutive fibroblast activation is responsible for organ fibrosis in fibrotic disorders including systemic sclerosis (SSc), but the underlying mechanisms are not fully understood, and effective therapies are lacking. We investigated the expression of the mitochondrial deacetylase sirtuin 3 (SIRT3) and its modulation by hexafluoro, a novel fluorinated synthetic honokiol analogue, in the conte...

From Department of Biomolecular Chemistry and the Wisconsin Institute Discovery, University of Wisconsin-­‐Madison, Madison, Wisconsin 53715 Running head: Sirt3 Deacetylates IDH2 and regulates redox status Address correspondence to: John M. Denu Ph.D., 2140 Wisconsin Institute of Discovery, 330 N Orchard Street, Madison, WI 53715. Fax: 608-­‐316-­‐4602; E-­‐mail: [email protected] Background: NA...

Lysine acetylation is a posttranslational modification that is dynamically regulated by the activity of acetyltransferases and deacetylases. The human and mouse genomes encode 18 different lysine deacetylases (KDACs) which are key regulators of many cellular processes. Identifying substrates of KDACs and pinpointing the regulated acetylation sites on target proteins may provide important inform...

In the 20th century, our knowledge of posttranslational modifications (PTMs) and their impact on protein function/enzyme activity was largely confined to that of protein phosphorylation and their regulation via kinases and phosphatases. However, as our scientific tools have become more sophisticated, and as we have advanced our knowledge of cellular/molecular biology, which has further been aug...