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Autophagy, Nov 27 2023, | https://doi.org/10.1080/15548627.2023.2287925
TRIM22 facilitates autophagosome-lysosome fusion by mediating the association of GABARAPs and PLEKHM1
Hansol Heo1,a, Hyungsun Park2,a, Myung Shin Lee1, Jongyoon Kim2, Juyeong Kim1, Soon-Young Jung1, Sun Kyeon Kim2, Seongju Lee2, Jaerak Chang1,3
1Department of Biomedical Sciences, Ajou University School of Medicine, Suwon, Republic of Korea
2Department of Anatomy, College of Medicine, and Program in Biomedical Science & Engineering, Inha University, Incheon, Republic of Korea
3Department of Brain Science, Ajou University School of Medicine, Suwon, Republic of Korea
aThese authors contributed equally to this work.
*Correspondence: Seongju Lee, Jaerak Chang
Abstract
Tripartite motif (TRIM) proteins are a large family of E3 ubiquitin ligases implicated in antiviral defense systems, tumorigenesis, and protein quality control. TRIM proteins contribute to protein quality control by regulating the ubiquitin-proteasome system, endoplasmic reticulum-associated degradation, and macroautophagy/autophagy. However, the detailed mechanisms through which various TRIM proteins regulate downstream events have not yet been fully elucidated. Herein, we identified a novel function of TRIM22 in the regulation of autophagy. TRIM22 promotes autophagosome-lysosome fusion by mediating the association of GABARAP family proteins with PLEKHM1, thereby inducing the autophagic clearance of protein aggregates, independent of its E3 ubiquitin ligase activity. Furthermore, a TRIM22 variant associated with early-onset familial Alzheimer disease interferes with autophagosome-lysosome fusion and autophagic clearance. These findings suggest TRIM22 as a critical autophagic regulator that orchestrates autophagosome-lysosome fusion by scaffolding autophagy-related proteins, thus representing a potential therapeutic target in neurodegenerative diseases.
논문정보
- Research article
- 2023년 11월 (BRIC 등록일 2023-12-05)
- 국내 연구진
- 생명과학 > 세포생물학
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