Aging perturbs 26S proteasome assembly in Drosophila melanogaster.
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.
Vernace
Vita A
VA
Department of Biological Sciences, Hunter College of CUNY, 695 Park Ave., New York, NY 10021, USA.
Arnaud
Lisette
L
Schmidt-Glenewinkel
Thomas
T
Figueiredo-Pereira
Maria E
ME
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
D000255:Adenosine Triphosphate; D046988:Proteasome Endopeptidase Complex; C061553:ATP dependent 26S protease