Abstract:
:The acetylase inhibitor, spermidine and the deacetylase activator, resveratrol, both induce autophagy and prolong life span of the model organism Caenorhabditis elegans in an autophagydependent fashion. Based on these premises, we investigated the differences and similarities in spermidine and resveratrol-induced autophagy. The deacetylase sirtuin 1 (SIRT1) and its orthologs are required for the autophagy induction by resveratrol but dispensable for autophagy stimulation by spermidine in human cells, Saccharomyces cerevisiae and C. elegans. SIRT1 is also dispensable for life-span extension by spermidine. Mass spectrometry analysis of the human acetylproteome revealed that resveratrol and/or spermidine induce changes in the acetylation of 560 peptides corresponding to 375 different proteins. Among these, 170 proteins are part of the recently elucidated human autophagy protein network. Importantly, spermidine and resveratrol frequently affect the acetylation pattern in a similar fashion. In the cytoplasm, spermidine and resveratrol induce convergent protein de-acetylation more frequently than convergent acetylation, while in the nucleus, acetylation is dominantly triggered by both agents. We surmise that subtle and concerted alterations in the acetylproteome regulate autophagy at multiple levels.
journal_name
Autophagyjournal_title
Autophagyauthors
Mariño G,Morselli E,Bennetzen MV,Eisenberg T,Megalou E,Schroeder S,Cabrera S,Bénit P,Rustin P,Criollo A,Kepp O,Galluzzi L,Shen S,Malik SA,Maiuri MC,Horio Y,López-Otín C,Andersen JS,Tavernarakis N,Madeo F,Kroemer Gdoi
10.4161/auto.7.6.15191subject
Has Abstractpub_date
2011-06-01 00:00:00pages
647-9issue
6eissn
1554-8627issn
1554-8635pii
15191journal_volume
7pub_type
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