Mitochondria-targeted inhibitors of the human SIRT3 lysine deacetylase.

ABSTRACT: Sirtuin 3 (SIRT3) is the major protein lysine deacetylase in the mitochondria. This hydrolase regulates a wide range of metabolically involved enzymes and has been considered as a potential drug target in certain cancers. Investigation of pharmacological intervention has been challenging due to a lack of potent and selective inhibitors of SIRT3. Here, we developed a strategy for selective inhibition of SIRT3 in cells, over its structurally similar isozymes that localize primarily to the nucleus (SIRT1) and the cytosol (SIRT2). This was achieved by directing the inhibitors to the mitochondria through incorporation of mitochondria-targeting peptide sequences into the inhibitor structures. Our inhibitors exhibited excellent mitochondrial localization in HeLa cells as indicated by fluorophore-

SUBMITTER: Troelsen KS 

PROVIDER: S-EPMC8341665 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature