Optineurin is an adaptor protein for ubiquitinated substrates in Golgi membrane-associated degradation
Golgi membrane-associated degradation (GOMED) is a process that leading to the degradation of proteins that have passed through the trans-Golgi membranes upon Golgi stress. GOMED is morphologically similar to autophagy, but the substrates degraded are different, and they thus have different biological roles. Although the substrate recognition mechanism of autophagy has been clarified in detail, that of GOMED is completely unknown. Here we report that GOMED degrades its substrate proteins selectively via optineurin (OPTN), as we found that the degradation of GOMED substrates is s`uppressed by the loss of OPTN. OPTN binds to K33 polyubiquitin-tagged proteins that have passed through the Golgi, which are then incorporated into GOMED structures for eventual degradation. In vivo, GOMED is known to be involved in the removal of mitochondria from erythrocytes, and in Optn-deficient mice, mitochondria are not degraded by GOMED, resulting in the appearance of erythrocytes containing mitochondria. These findings provide insight into the substrate recognition mechanism of GOMED.
Authors
- Shigeomi Shimizu (ORCID: https://orcid.org/0000-0002-8437-0791)
- Hajime Tajima Sakurai (ORCID: https://orcid.org/0000-0001-7441-0203)
- Yoichi Nibe-Shirakihara (ORCID: https://orcid.org/0009-0005-9843-6674)
- Hideshi Kawakami (ORCID: https://orcid.org/0000-0002-1405-0901)
- Satoru Torii (ORCID: https://orcid.org/0000-0003-4841-7131)
- Shinya Honda (ORCID: https://orcid.org/0000-0003-3443-044X)
- Michael Lazarou (ORCID: https://orcid.org/0000-0003-2150-5545)
- Shigeru Oshima (ORCID: https://orcid.org/0000-0003-1186-9177)
- Ryuichi Okamoto (ORCID: https://orcid.org/0000-0002-7047-571X)
- Satoko Arakawa (ORCID: https://orcid.org/0000-0002-4375-1643)
- Hirofumi Yamaguchi
Institutions
- Hiroshima University (JP)
- Tokyo Medical and Dental University (JP)
- The University of Melbourne (AU)
- Walter and Eliza Hall Institute of Medical Research (AU)
- Shimizu (Japan) (JP)
- Australian Regenerative Medicine Institute (AU)
- Sasaki Institute (JP)
- Japan Chemical Innovation and Inspection Institute (JP)
- Monash University (AU)
- The University of Tokyo (JP)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-10-20
- DOI
- https://doi.org/10.1038/s41467-025-64400-3
- Citations
- 1
- Primary Topic
- Autophagy in Disease and Therapy
- Type
- article
- Field-Weighted Citation Impact
- 1.35
Funders
- Japan Agency for Medical Research and Development
- Ministry of Education, Culture, Sports, Science and Technology
- Medical Research Council
- National Health and Medical Research Council
- Japan Society for the Promotion of Science
- Core Research for Evolutional Science and Technology