Longevity-relevant regulation of autophagy at the level of the acetylproteome

Guillermo Mariño, Eugenia Morselli, Martin V Bennetzen, Tobias Eisenberg, Evgenia Megalou, Sabrina Schroeder, Sandra Cabrera, Paule Bénit, Pierre Rustin, Alfredo Criollo, Oliver Kepp, Lorenzo Galluzzi, Shensi Shen, Shoaib A Malik, Maria Chiara Maiuri, Yoshiyuki Horio, Carlos López-Otín, Jens S. Andersen, Nektarios Tavernarakis, Frank MadeoGuido Kroemer

Research output: Contribution to journalJournal articleResearchpeer-review

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.
Original languageEnglish
JournalAutophagy
Volume7
Issue number6
Pages (from-to)647-9
Number of pages3
ISSN1554-8627
DOIs
Publication statusPublished - 1. Jun 2011

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