The Cys-N-degron pathway modulates pexophagy through the N-terminal oxidation and arginylation of ACAD10.

ABSTRACT: In the N-degron pathway, N-recognins recognize cognate substrates for degradation via the ubiquitin (Ub)-proteasome system (UPS) or the autophagy-lysosome system (hereafter autophagy). We have recently shown that the autophagy receptor SQSTM1/p62 (sequestosome 1) is an N-recognin that binds the N-terminal arginine (Nt-Arg) as an N-degron to modulate autophagic proteolysis. Here, we show that the N-degron pathway mediates pexophagy, in which damaged peroxisomal fragments are degraded by autophagy under normal and oxidative stress conditions. This degradative process initiates when the Nt-Cys of ACAD10 (acyl-CoA dehydrogenase family, member 10), a receptor in pexophagy, is oxidized into Cys sulfinic (Cys^O2) or sulfonic acid (Cys^O3) by ADO (2-aminoethanethiol (cysteamine

SUBMITTER: Shim SM 

PROVIDER: S-EPMC10262816 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature