title: Nϵ-lysine acetylation in the lumen of the endoplasmic reticulum: A way to regulate autophagy and maintain protein homeostasis in the secretory pathway.
abstract: The Nϵ-lysine acetylation of cargo proteins in the lumen of the endoplasmic reticulum (ER) requires a membrane transporter (SLC33A1) and 2 acetyltransferases (NAT8B and NAT8). The ER acetylation machinery regulates the homeostatic balance between quality control/efficiency of the secretory pathway and autophagy-mediated disposal of toxic protein aggregates. We recently reported that the autophagy pathway that acts downstream of the ER acetylation machinery specifically targets protein aggregates that form within the secretory pathway. Genetic and biochemical manipulation of ER acetylation in a mouse model of Alzheimer disease is able to restore normal proteostasis and rescue the disease phenotype. Here we summarize these findings and offer an overview of the ER-acetylation machinery.
authors.affiliation: a Department of Medicine , University of Wisconsin-Madison , Madison , WI , USA.
authors.forename: Yajing
authors.initials: Y
authors.lastname: Peng
authors.affiliation: a Department of Medicine , University of Wisconsin-Madison , Madison , WI , USA.|b Department of Neuroscience , University of Wisconsin-Madison , Madison , WI , USA.|c Geriatric Research Education Clinical Center, VA Medical Center , Madison , WI , USA.
authors.forename: Luigi
authors.initials: L
authors.lastname: Puglielli
mesh_terms: D000107:Acetylation; D000818:Animals; D001343:Autophagy; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D006706:Homeostasis; D006801:Humans; D008954:Models, Biological; D011506:Proteins / Q000378:metabolism*; D055571:Secretory Pathway
chemical_list: D011506:Proteins
keywords: acetyl-CoA; autophagy; endoplasmic reticulum; lysine acetylation; secretory pathway