title: Aging perturbs 26S proteasome assembly in Drosophila melanogaster.
abstract: 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 (approximately 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.
authors.affiliation: Department of Biological Sciences, Hunter College of CUNY, 695 Park Ave., New York, NY 10021, USA.
authors.forename: Vita A
authors.initials: VA
authors.lastname: Vernace
authors.forename: Lisette
authors.initials: L
authors.lastname: Arnaud
authors.forename: Thomas
authors.initials: T
authors.lastname: Schmidt-Glenewinkel
authors.forename: Maria E
authors.initials: ME
authors.lastname: Figueiredo-Pereira
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000375:Aging / Q000502:physiology*; D000818:Animals; D015153:Blotting, Western; D003600:Cytosol / Q000201:enzymology; D004331:Drosophila melanogaster / Q000254:growth & development / Q000378:metabolism*; D005260:Female; D008297:Male; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D013997:Time Factors
chemical_list: D000255:Adenosine Triphosphate; D046988:Proteasome Endopeptidase Complex; C061553:ATP dependent 26S protease