title: Longevity-relevant regulation of autophagy at the level of the acetylproteome.
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.
authors: INSERM, U, Institut Gustave Roussy, Université Paris Sud, Villejuif, France.
authors: Guillermo
authors: G
authors: Mariño
authors: Eugenia
authors: E
authors: Morselli
authors: Martin V
authors: MV
authors: Bennetzen
authors: Tobias
authors: T
authors: Eisenberg
authors: Evgenia
authors: E
authors: Megalou
authors: Sabrina
authors: S
authors: Schroeder
authors: Sandra
authors: S
authors: Cabrera
authors: Paule
authors: P
authors: Bénit
authors: Pierre
authors: P
authors: Rustin
authors: Alfredo
authors: A
authors: Criollo
authors: Oliver
authors: O
authors: Kepp
authors: Lorenzo
authors: L
authors: Galluzzi
authors: Shensi
authors: S
authors: Shen
authors: Shoaib A
authors: SA
authors: Malik
authors: Maria Chiara
authors: MC
authors: Maiuri
authors: Yoshiyuki
authors: Y
authors: Horio
authors: Carlos
authors: C
authors: López-Otín
authors: Jens S
authors: JS
authors: Andersen
authors: Nektarios
authors: N
authors: Tavernarakis
authors: Frank
authors: F
authors: Madeo
authors: Guido
authors: G
authors: Kroemer
mesh_terms: D000107:Acetylation; D000818:Animals; D001343:Autophagy; D017173:Caenorhabditis elegans / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D004331:Drosophila melanogaster; D006801:Humans; D008136:Longevity / Q000502:physiology*; D020543:Proteome; D040901:Proteomics / Q000379:methods*; D000077185:Resveratrol; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D056564:Sirtuin 1 / Q000378:metabolism; D013095:Spermidine / Q000378:metabolism; D013267:Stilbenes / Q000378:metabolism; D013347:Subcellular Fractions
chemical_list: D020543:Proteome; D013267:Stilbenes; C447939:SIRT1 protein, human; D056564:Sirtuin 1; D000077185:Resveratrol; D013095:Spermidine