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SIRT3 is pro-apoptotic and participates in distinct basal apoptotic pathways

Allison, Simon J. and Milner, Jo (2007) SIRT3 is pro-apoptotic and participates in distinct basal apoptotic pathways. Cell Cycle, 6 (21). pp. 2669-2677. ISSN 1538-4101

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Abstract

SIRT3, one of seven mammalian sirtuins, is a NAD-dependent deacetylase. SIRT3 localizes to mitochondria where it deacetylates and thus activates acetyl-CoA synthetase 2 (AceCS2), indicating a role for SIRT3 in metabolism. Here we provide evidence that SIRT3 also impacts upon apoptosis and cell growth control. Using RNAi under basal (non-stress) conditions we show that SIRT3 is required for apoptosis induced by selective silencing of Bcl-2 in HCT116 human epithelial cancer cells. Identical treatment of ARPE19 epithelial non-cancer cells induces G(1) growth arrest which also proved to be SIRT3-dependent. Previously we have identified SIRT1 and JNK2 as constitutive suppressors of apoptosis in HCT116 cells. We now demonstrate that SIRT3 functions in JNK2-regulated apoptosis but is dispensable for SIRT1-regulated apoptosis. SIRT3 is also dispensable for stress-induced apoptosis. Thus the pro-apoptotic functioning of SIRT3 is selectively coupled with defined pathways regulating cell survival under basal conditions.

Item Type: Article
Subjects: Q Science > Q Science (General)
Schools: School of Applied Sciences
Depositing User: Elizabeth Boulton
Date Deposited: 01 Mar 2016 15:37
Last Modified: 01 Mar 2016 15:37
URI: http://eprints.hud.ac.uk/id/eprint/27410

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