Aging perturbs 26S proteasome assembly in Drosophila melanogaster Vita A. Vernace, Lisette Arnaud, Thomas Schmidt-Glenewinkel 1 and Maria E. Figueiredo-Pereira 1 Department of Biological Sciences, Hunter College of the City University of New York, New York, USA 1 Correspondence: Department of Biological Sciences, Hunter College of CUNY, 695 Park Ave., New York, N.Y. 10021, USA. E-mails: pereira@genectr.hunter.cuny.edu and thomas@genectr.hunter.cuny.edu Aging is associated with loss of quality control in protein turnover. The ubiquitin-proteasome pathway is critical to this quality control process as it degrades mutated and damaged proteins. We identified a unique aging-dependent mechanism that contributes to proteasome dysfunction in Drosophila melanogaster . Our studies are the first to show that the major proteasome form in old (43–47 days old) female and male flies is the weakly active 20S core particle, while in younger (1–32 days old) flies highly active 26S proteasomes are preponderant. Old (43–47 days) flies of both genders also exhibit a decline (∼50%) in ATP levels, which is relevant to 26S proteasomes, as their assembly is ATP-dependent. The steep declines in 26S proteasome and ATP levels were observed at an age (43–47 days) when the flies exhibited a marked drop in locomotor performance, attesting that these are "old age" events. Remarkably, treatment with a proteasome inhibitor increases ubiquitinated protein levels and shortens the life span of old but not young flies. In conclusion, our data reveal a previously unknown mechanism that perturbs proteasome activity in "old-age" female and male Drosophila most likely depriving them of the ability to effectively cope with proteotoxic damages caused by environmental and/or genetic factors.—Vernace, V. A., Arnaud, L., Schmidt-Glenewinkel, T., Figueiredo-Pereira, M. E. Aging perturbs 26S proteasome assembly in Drosophila melanogaster . Key Words: ubiquitin • protein degradation • 26S/20S proteasomes • ATP depletion • fly aging
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Aging perturbs 26S proteasome assembly in Drosophila melanogaster
Vernace, Vita A.; Arnaud, Lisette; Schmidt-Glenewinkel, Thomas; Figueiredo-Pereira, Maria E.
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, Volume 21 (11): 2672
Fed of American Socs for Experimental Biology – Sep 1, 2007
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