OPTN (optineurin)-mediated selective substrate recognition in Golgi membrane-associated degradation

Golgi membrane-associated degradation (GOMED) is a protein degradation pathway that primarily targets proteins transiting through the trans-Golgi cisternae, and functions constitutively or in response to abnormalities in Golgi-trafficked cargos. Although GOMED is morphologically similar to macroautophagy/autophagy, its substrate recognition mechanism has remained unclear to date. In this study, we identified OPTN (optineurin) as an essential receptor protein for selective cargo recognition in GOMED. We found that OPTN binds K33-linked polyubiquitinated proteins that have passed through the Golgi apparatus and delivers them to GOMED structures for degradation. In vivo, OPTN-dependent GOMED is required for mitochondrial clearance during erythrocyte maturation, and Optn-deficient mice have erythrocytes that retain mitochondria. Taken together, our findings define the molecular basis of selective cargo recognition in GOMED.