Nε-lysine acetylation in the endoplasmic reticulum – a novel cellular mechanism that regulates proteostasis and autophagy

Protein post-translational modifications (PTMs) take many shapes, have many effects and are necessary for cellular homeostasis. One of these PTMs, Nε-lysine acetylation, was thought to occur only in the mitochondria, cytosol and nucleus, but this paradigm was challenged in the past decade with the discovery of lysine acetylation in the lumen of the endoplasmic reticulum (ER). This process is governed by the ER acetylation machinery: the cytosol:ER-lumen acetyl-CoA transporter AT-1 (also known as SLC33A1), and the ER-resident lysine acetyltransferases ATase1 and ATase2 (also known as NAT8B and NAT8, respectively). This Review summarizes the more recent biochemical, cellular and mouse model studies that underscore the importance of the ER acetylation process in maintaining protein homeostasis and autophagy within the secretory pathway, and its impact on developmental and age-associated diseases.