Gladstone Institute

Regulation of GST Protein Function by Reversible Acetylation: Role of SIRT3

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Recent insights into the molecular mechanisms of aging have provided greater knowledge into why and how we age. Revealing the key players in these complex pathways will ultimately lead to a broader understanding, and will potentially lead to therapeutics to prevent age-related diseases and to enhance longevity. A family of proteins called sirtuins has recently been shown to be involved in longevity pathways, and have numerous targets with varying degrees of regulation. The key to understanding longevity pathways is to understand the control sirtuins have over their various substrates.

SIRT3 is a mitochondrial sirtuin and is the major mitochondrial protein deacetylase. Work in the Verdin Lab has illustrated the important role of SIRT3 in the control of mitochondrial metabolism. We have identified SIRT3 substrates involved in ATP production, fat burning, sterol metabolism and redox regulation. We are currently studying the regulation of these substrates and defining the role of protein acetylation in various mitochondrial functions.