PEX14 acts as a molecular link between optineurin and the autophagic machinery to induce pexophagy

ABSTRACT: Peroxisome degradation, known as pexophagy, is essential for eliminating surplus and dysfunctional peroxisomes, with dysregulation linked to various diseases. Previous research revealed that ectopic expression of optineurin (OPTN), a versatile autophagy adaptor involved in multiple autophagic pathways (e.g., mitophagy, aggrephagy, and xenophagy), triggers pexophagy in HEK-293 cells. However, the underlying mechanism remained elusive. Here, we demonstrate that OPTN-mediated pexophagy is a cell type-specific process. In addition, using proximity labeling, we identified PEX14, a peroxisomal membrane protein, as an OPTN-interacting partner. GFP-Trap analyses confirmed this interaction and revealed that PEX14 and OPTN interact through their respective coiled-coil and C-terminal ubiquitin-binding domains, independently of ubiquitin. Furthermore, our results indicate that the C-terminal half of OPTN-GFP induces pexophagy by oligomerization with endogenous OPTN. Overall, these findings propose PEX14 as a docking factor for OPTN at the peroxisomal membrane, facilitating the connection between peroxisomes and the autophagic membrane scaffold during OPTN-mediated pexophagy.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture

SUBMITTER: Li Hongli  

LAB HEAD: Marc Fransen

PROVIDER: PXD053489 | Pride | 2025-09-23

REPOSITORIES: Pride