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Acetyl-coenzyme A synthetase 2 is a nuclear protein required for replicative longevity in Saccharomyces cerevisiae

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Abstract

Acs2p is one of two acetyl-coenzyme A synthetases in Saccharomyces cerevisiae. We have prepared and characterized a monoclonal antibody specific for Acs2p and find that Acs2p is localized primarily to the nucleus, including the nucleolus, with a minor amount in the cytosol. We find that Acs2p is required for replicative longevity: an acs2∆ strain has a reduced replicative life span compared to wild-type and acs1∆ strains. Furthermore, replicatively aged acs2∆ cells contain elevated levels of extrachromosomal rDNA circles, and silencing at the rDNA locus is impaired in an acs2∆ strain. These findings indicate that Acs2p-mediated synthesis of acetyl-CoA in the nucleus functions to promote rDNA silencing and replicative longevity in yeast.

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Acknowledgments

Strains T2-3D, GG621, and GG625 were kindly provided by Raymond Brandt and H. Yde Steensma, Leiden University. Proteolytic fragmentation and mass spectrometry were done by Scott H. McClung and Stanley M. Stevens at the University of Florida Interdisciplinary Center for Biotechnology Research (UF ICBR). This study was supported by the Ellison Medical Foundation grant AG-NO-0014 to AAF and the NIH grant AG023719 to JPA.

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  1. Alaric A. Falcón

    Present address: Department of Nutritional Sciences and Toxicology, University of California, Berkeley, CA, 94720, USA

Authors and Affiliations

  1. Department of Anatomy and Cell Biology, Health Science Center, University of Florida, Gainesville, FL, 32610-0235, USA

    Alaric A. Falcón, Shaoping Chen, Michael S. Wood & John P. Aris

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  1. Alaric A. Falcón
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Correspondence to John P. Aris.

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Falcón, A.A., Chen, S., Wood, M.S. et al. Acetyl-coenzyme A synthetase 2 is a nuclear protein required for replicative longevity in Saccharomyces cerevisiae . Mol Cell Biochem 333, 99–108 (2010). https://doi.org/10.1007/s11010-009-0209-z

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