Abstract
Posttranslational modification (PTM) is pivotal for regulating protein functions. Compared to acetylation on lysine residues, the functions and molecular mechanisms of N-terminal acetylation that occur on the first amino acids of proteins are less understood in the macroautophagy/autophagy field. We recently demonstrated that the B-type N-terminal acetyltransferase NatB, formed by the catalytic subunit Nat3 and auxiliary subunit Mdm20, is essential for autophagy. Deficiency of NatB causes blockage of autophagosome formation. We further identified the actin cytoskeleton constituent Act1 and dynamin-like GTPase Vps1 as substrates modified by NatB. The N-terminal acetylation of Act1 promotes its formation of actin filaments and thus facilitates trafficking of Atg9-containing vesicles for autophagosome formation, whereas N-terminal acetylation of Vps1 promotes its interaction with SNARE proteins and facilitates autophagosome-vacuole fusion. Restoring the N-terminal acetylation of Act and Vps1 does not restore autophagy in NatB-deleted cells, suggesting that additional substrates of NatB modification are involved in autophagy regulation.