Before import: N-terminal acetylation at the interface of plastid protein targeting and proteostasis.

Most chloroplast proteins are synthesized in the cytosol as precursor proteins carrying N-terminal transit peptides that mediate post-translational import into the organelle. During this transient cytosolic phase, precursor proteins are exposed to the cellular N-terminal processing machinery, including methionine aminopeptidases and N-terminal acetyltransferases (NATs). Recent proteomic studies have provided direct evidence that plastid precursor proteins undergo N-terminal acetylation prior to import, establishing a previously unrecognized link between co-translational processing and plastid protein targeting. Here, we review current knowledge of N-terminal processing of plastid precursor proteins, including sequence determinants, NAT specificity, and experimental evidence for precursor acetylation in vivo. We discuss how precursor acetylation may influence precursor fate by affecting protein stability, import competence, and cytosolic quality-control pathways. Finally, we propose that the high prevalence of NatA-compatible plastid precursor proteins may reflect evolutionary constraints imposed on transit peptide architecture by organelle targeting and import. Understanding how N-terminal processing intersects with precursor protein targeting will provide new insights into the regulation of plastid biogenesis and cytosolic proteostasis in plants.