Translophagy—A potential link between autophagy impairment and translational errors
Maintenance of protein homeostasis requires coordination between protein synthesis and degradation, yet whether autophagy directly controls translational machinery remains unclear. Here we explored whether autophagy maintains translational fidelity. Proteomic analysis of ubiquitin-enriched fractions and p62-associated proteins in autophagy-deficient tissue confirmed previous studies identifying ribosomal proteins and RNA-binding factors among candidate autophagy cargo. Pharmacological or genetic impairment of autophagy increased translational errors, particularly during oxidative stress. Components of the translational machinery localised to LC3-positive autophagic structures and accumulated in human brain tissue affected by neurodegeneration. These findings support a hypothesis in which autophagy preserves protein synthesis quality by removing damaged translational machinery. We term this proposed mechanism translophagy, potentially linking autophagy dysfunction, oxidative stress and the aberrant proteins in neurodegenerative disease.
Authors
- Diego Manni
- Gailing Ma
- Tetsushi Kataura (ORCID: https://orcid.org/0000-0002-3958-5232)
- Daniel Erskine (ORCID: https://orcid.org/0000-0002-1752-5343)
- Marco Trevisán-Herraz (ORCID: https://orcid.org/0000-0002-7129-0602)
- Robin Antrobus (ORCID: https://orcid.org/0000-0001-8608-4011)
- Max Brown
- Masaaki Komatsu (ORCID: https://orcid.org/0000-0001-7672-7722)
- Viktor I. Korolchuk (ORCID: https://orcid.org/0000-0002-4071-592X)
- Gavin D. Richardson (ORCID: https://orcid.org/0000-0002-2310-9987)
- Mykola V. Korolchuk
- Mustafa Khwaja
Institutions
- University of Tsukuba (JP)
- University of Cambridge (GB)
- Juntendo University (JP)
- Royal Surrey NHS Foundation Trust (GB)
- Newcastle Hospitals - Campus for Ageing and Vitality (GB)
- Institute of Applied Biochemistry (JP)
- Procter & Gamble (United States) (US)
- Newcastle University (GB)
Publication Details
- Journal
- FEBS Letters
- Published
- 2026-08-27
- DOI
- https://doi.org/10.1002/1873-3468.70448
- Primary Topic
- Autophagy in Disease and Therapy
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Procter and Gamble
- Sumitomo Foundation
- Uehara Memorial Foundation
- Japan Agency for Medical Research and Development
- Nippon Shinyaku
- Alzheimer’s Research UK
- Senri Life Science Foundation
- Lotte Foundation
- Medical Research Council
- Biotechnology and Biological Sciences Research Council
- Japan Society for the Promotion of Science